)| PMID |
18513389 ( ) |
|---|---|
| Title | New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background. |
| Abstract | BACKGROUND: Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis RESULTS: Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial nitric oxide synthase 690 C/T and glu298asp; vitamin K-dependent coagulation factor seven arg353glu, glycoprotein Ia/IIa 873 G/A and E-selectin ser128arg. CONCLUSION: This study provides an alternative and reliable method to approach complex diseases. Indeed, the application of a novel artificial intelligence-based method offers a new insight into genetic markers of sporadic ALS pointing out the existence of a strong genetic background. Niguarda Ca' Granda Hospital P.za Ospedale Maggiore 3, 20100 Milan, Italy. silvana.penco@ospedaleniguarda.it |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 15 | TNFalpha | tumor necrosis factor alpha | tnf alpha | TNF | |
| 9204 | PON1 | paraoxonase 1 | 10 | PON | PON1 | paraoxonase | paraoxonase 1 | |
| 613 | APOE | apolipoprotein E | 7 | APOE | apolipoprotein e | ApoE | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 7 | superoxide dismutase 1 | SOD1 | |
| 10718 | SELE | selectin E (endothelial adhesion molecule 1) | 6 | SELE | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 5 | NOS3 | endothelial nitric oxide synthase | |
| 336 | AGTR1 | angiotensin II receptor, type 1 | 4 | angiotensin ii receptor | AGTR1 | angiotensin ii receptor type1 | |
| 7939 | NPPA | natriuretic peptide precursor A | 4 | atrial natriuretic peptide | NPPA | |
| 6677 | LPL | lipoprotein lipase | 4 | LPL | lipoprotein lipase | |
| 9205 | PON2 | paraoxonase 2 | 4 | paraoxonase 2 | PON2 | |
| 288 | ADRB3 | adrenergic, beta-3-, receptor | 3 | ADRB3 | beta 3 adrenergic receptor | |
| 602 | APOA4 | apolipoprotein A-IV | 3 | APOA4 | |
| 6547 | LDLR | low density lipoprotein receptor (familial hypercholesterolemia) | 3 | low density lipoprotein receptor | LDLR | |
| 6619 | LIPC | lipase, hepatic | 3 | LIPC | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 3 | NOS | |
| 4400 | GNB3 | guanine nucleotide binding protein (G protein), beta polypeptide 3 | 3 | g protein beta 3 subunit | GNB3 | |
| 286 | ADRB2 | adrenergic, beta-2-, receptor, surface | 3 | beta 2 adrenergic receptor | ADRB2 | |
| 7436 | MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | 3 | MTHFR | methylenetetrahydrofolate reductase | |
| 1869 | CETP | cholesteryl ester transfer protein, plasma | 3 | CETP | cholesteryl ester transfer protein | |
| 10599 | SCNN1A | sodium channel, nonvoltage-gated 1 alpha | 2 | SCNN1A | |
| 7173 | MMP3 | matrix metallopeptidase 3 (stromelysin 1, progelatinase) | 2 | MMP3 | mmp3 | |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | 2 | manganese superoxide dismutase | SOD2 | |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | 2 | peroxisome proliferator activated receptor gamma | PPARG | |
| 610 | APOC3 | apolipoprotein C-III | 2 | APOC3 | |
| 3662 | FGB | fibrinogen beta chain | 2 | FGB | |
| 6156 | ITGB3 | integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) | 1 | ITGB3 | |
| 2625 | CYP2D6 | cytochrome P450, family 2, subfamily D, polypeptide 6 | 1 | CYP2D6 | |
| 3544 | F7 | coagulation factor VII (serum prothrombin conversion accelerator) | 1 | factor vii | |
| 9461 | PRPH | peripherin | 1 | peripherin | |
| 2169 | CNTF | ciliary neurotrophic factor | 1 | ciliary neurotrophic factor | |
| 243 | ADD1 | adducin 1 (alpha) | 1 | ADD1 | |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | 1 | DCP1 | |
| 1550 | CBS | cystathionine-beta-synthase | 1 | CBS | |
| 17889 | APEX2 | APEX nuclease (apurinic/apyrimidinic endonuclease) 2 | 1 | APEX | |
| 2615 | CYP2B6 | cytochrome P450, family 2, subfamily B, polypeptide 6 | 1 | P450 | |
| 4886 | HFE | hemochromatosis | 1 | HFE | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 1 | AGT | |
| 1361 | C9orf3 | chromosome 9 open reading frame 3 | 1 | APO | |
| 6709 | LTA | lymphotoxin alpha (TNF superfamily, member 1) | 1 | tumor necrosis factor beta | |
| 6667 | LPA | lipoprotein, Lp(a) | 1 | LPA | |
| 11609 | TBXAS1 | thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) | 1 | cytochrome p450 | |
| 603 | APOB | apolipoprotein B (including Ag(x) antigen) | 1 | APOB | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.2 | gene coding for copper/zinc copper zinc superoxide dismutase 1 (SOD1) SOD1 appears to be mutated in 10_amp_#x02013 20% in the familial |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.2 | been extensively studied and some major genes in addition to SOD1 have been recognised as being responsible for the monogenic inheritance |
| 2615 | CYP2B6 | cytochrome P450, family 2, subfamily B, polypeptide 6 | P450 | 1.9 | 4 genotype excitotoxicity genes ciliary neurotrophic factor (CTNF), CTNF cytochrome P450 debrisoquine hydroxylase CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese |
| 2625 | CYP2D6 | cytochrome P450, family 2, subfamily D, polypeptide 6 | CYP2D6 | 1.2 | genes ciliary neurotrophic factor (CTNF), CTNF cytochrome P450 debrisoquine hydroxylase CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese superoxide dismutase SOD2 |
| 17889 | APEX2 | APEX nuclease (apurinic/apyrimidinic endonuclease) 2 | APEX | 0.3 | CTNF cytochrome P450 debrisoquine hydroxylase CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese superoxide dismutase SOD2 monoamine oxidase allele B and |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | SOD2 | 0.9 | CYP2D6 apurinic apyrimidinic endonuclease (APEX), APEX mitochondrial manganese superoxide dismutase SOD2 monoamine oxidase allele B and paraoxonases have been reported in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.2 | of the family and when no mutations were present in SOD1 gene |
| 6667 | LPA | lipoprotein, Lp(a) | LPA | 0.3 | The following polymorphisms (SNPs) SNPs were genotyped LPA 93C/T, 93C T 121 G/A, G A APOA4 thr347ser glu360his |
| 602 | APOA4 | apolipoprotein A-IV | APOA4 | 0.3 | were genotyped LPA 93C/T, 93C T 121 G/A, G A APOA4 thr347ser glu360his APOBthr71ile APOC3 641C/A, 641C A 482C/T, 482C T |
| 610 | APOC3 | apolipoprotein C-III | APOC3 | 0.3 | 93C T 121 G/A, G A APOA4 thr347ser glu360his APOBthr71ile APOC3 641C/A, 641C A 482C/T, 482C T 455 T/C, T C |
| 613 | APOE | apolipoprotein E | APOE | 1.3 | C T 3175 C/G, C G 3206 T/G, T G APOE cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T |
| 288 | ADRB3 | adrenergic, beta-3-, receptor | ADRB3 | 1.6 | C/G, C G 3206 T/G, T G APOE cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T LPL 93 T/G, |
| 6619 | LIPC | lipase, hepatic | LIPC | 0.6 | T/G, T G APOE cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T LPL 93 T/G, T G asp9asn asn291ser |
| 6677 | LPL | lipoprotein lipase | LPL | 1.6 | cys112arg arg158cys ADRB3 trp64arg PPAR_amp_#x003b3 pro12ala LIPC 480C/T, 480C T LPL 93 T/G, T G asp9asn asn291ser ser447term PON1 met55leu gln192arg |
| 9204 | PON1 | paraoxonase 1 | PON1 | 1.8 | 480C T LPL 93 T/G, T G asp9asn asn291ser ser447term PON1 met55leu gln192arg PON2 ser311cys LDLR NcoI+/-, NcoI - CETP-631C/A, CETP-631C |
| 9205 | PON2 | paraoxonase 2 | PON2 | 1.3 | 93 T/G, T G asp9asn asn291ser ser447term PON1 met55leu gln192arg PON2 ser311cys LDLR NcoI+/-, NcoI - CETP-631C/A, CETP-631C A -629 C/A, |
| 6547 | LDLR | low density lipoprotein receptor (familial hypercholesterolemia) | LDLR | 1.8 | T G asp9asn asn291ser ser447term PON1 met55leu gln192arg PON2 ser311cys LDLR NcoI+/-, NcoI - CETP-631C/A, CETP-631C A -629 C/A, C A |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | NcoI - CETP-631C/A, CETP-631C A -629 C/A, C A ile405val TNF beta thr26asn MTHFR 677 C/T, C T NOS3 -922 A/G, |
| 7436 | MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | MTHFR | 0.3 | CETP-631C A -629 C/A, C A ile405val TNF beta thr26asn MTHFR 677 C/T, C T NOS3 -922 A/G, A G -690 |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | NOS3 | 1.2 | A ile405val TNF beta thr26asn MTHFR 677 C/T, C T NOS3 -922 A/G, A G -690 C/T, C T glu298asp DCP1 |
| 2707 | ACE | angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 | DCP1 | 1.3 | NOS3 -922 A/G, A G -690 C/T, C T glu298asp DCP1 IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr |
| 336 | AGTR1 | angiotensin II receptor, type 1 | AGTR1 | 0.9 | -690 C/T, C T glu298asp DCP1 IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A |
| 7939 | NPPA | natriuretic peptide precursor A | NPPA | 0.9 | IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A NPPA 2238 T/C, T C ADD1 |
| 7939 | NPPA | natriuretic peptide precursor A | NPPA | 0.9 | 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 |
| 10599 | SCNN1A | sodium channel, nonvoltage-gated 1 alpha | SCNN1A | 0.3 | G/A, G A NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 |
| 4400 | GNB3 | guanine nucleotide binding protein (G protein), beta polypeptide 3 | GNB3 | 0.3 | NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) |
| 286 | ADRB2 | adrenergic, beta-2-, receptor, surface | ADRB2 | 1.6 | ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) -1171 5A/6A, 5A 6A FII |
| 286 | ADRB2 | adrenergic, beta-2-, receptor, surface | ADRB2 | 1.6 | SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) -1171 5A/6A, 5A 6A FII 20210 G/A, |
| 7173 | MMP3 | matrix metallopeptidase 3 (stromelysin 1, progelatinase) | MMP3 | 0.3 | ala663thr GNB3 825 C/T, C T ADRB2 arg16gly ADRB2 gln27glu MMP3 (-1171) -1171 5A/6A, 5A 6A FII 20210 G/A, G A |
| 3662 | FGB | fibrinogen beta chain | FGB | 0.3 | arg353glu PAI -675 G5/G4, G5 G4 11053 G/T, G T FGB -455 G/A, G A ITGA2 873 G/A, G A ITGB3 |
| 10718 | SELE | selectin E (endothelial adhesion molecule 1) | SELE | 0.6 | G/A, G A ITGA2 873 G/A, G A ITGB3 leu33pro SELE ser128arg leu554phe ICAM gly214arg TNF alpha -376 G/A, G A |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | G/A, G A ITGB3 leu33pro SELE ser128arg leu554phe ICAM gly214arg TNF alpha -376 G/A, G A -308G/A, -308G A -244 G/A, |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | AGT | 0.2 | glu298asp DCP1 IVS16 ins/del, ins del AGTR1 1166A/C, 1166A C AGT met235thr NPPA 664 G/A, G A NPPA 2238 T/C, T |
| 243 | ADD1 | adducin 1 (alpha) | ADD1 | 0.1 | NPPA 664 G/A, G A NPPA 2238 T/C, T C ADD1 gly460trp SCNN1A trp493arg ala663thr GNB3 825 C/T, C T ADRB2 |
| 6156 | ITGB3 | integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) | ITGB3 | 0.1 | FGB -455 G/A, G A ITGA2 873 G/A, G A ITGB3 leu33pro SELE ser128arg leu554phe ICAM gly214arg TNF alpha -376 G/A, |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | The marker TNF beta thr26asn is twice present in the arrays as a |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.2 | All ALS subjects were screened for SOD1 mutation through PCR amplification and direct sequencing according to standard |
| 603 | APOB | apolipoprotein B (including Ag(x) antigen) | APOB | 0.6 | those markers for which only one genotype was present (APOB APOB Arg3500Gln CBS Ile278Thr CETP Asp442Gly 14G(+1) 14G 1 A and |
| 1869 | CETP | cholesteryl ester transfer protein, plasma | CETP | 1.8 | only one genotype was present (APOB APOB Arg3500Gln CBS Ile278Thr CETP Asp442Gly 14G(+1) 14G 1 A and 14(+3) 14 3 T |
| 1550 | CBS | cystathionine-beta-synthase | CBS | 0.2 | for which only one genotype was present (APOB APOB Arg3500Gln CBS Ile278Thr CETP Asp442Gly 14G(+1) 14G 1 A and 14(+3) 14 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.2 | All patients were previously screened for SOD1 gene mutation by sequence analysis and no genetic variations were |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | procedure (multiplex multiplex and hybridization steps was checked by the TNF beta thr26asn polymorphism that gave the same results in both |
| 613 | APOE | apolipoprotein E | APOE | 1.3 | independently selected by the five TWIST procedures apolipoprotein E (APOE) APOE (chromosome chromosome 19q13.2 arg158cys hepatic lipase (LIPC) LIPC (chromosome chromosome |
| 6619 | LIPC | lipase, hepatic | LIPC | 0.6 | E (APOE) APOE (chromosome chromosome 19q13.2 arg158cys hepatic lipase (LIPC) LIPC (chromosome chromosome 15q21-23 -480 C/T; C T endothelial nitric oxide |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | NOS3 | 1.2 | 15q21-23 -480 C/T; C T endothelial nitric oxide synthase (NOS3) NOS3 (chromosome chromosome 7q36 690 C/T C T and glu298asp vitamin |
| 10718 | SELE | selectin E (endothelial adhesion molecule 1) | SELE | 0.6 | ITGA2 (chromosome chromosome 5q23-q31 873 G/A; G A E-selectin (SELE) SELE (chromosome chromosome 1q22-q25 ser128arg |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | PPARG | 2.2 | five experiments consisted of peroxisome proliferator activated receptor gamma (PPARG) PPARG pro12ala (chromosome chromosome 3p25 lipoprotein lipase (LPL) LPL asp9asn (chromosome |
| 6677 | LPL | lipoprotein lipase | LPL | 1.6 | gamma (PPARG) PPARG pro12ala (chromosome chromosome 3p25 lipoprotein lipase (LPL) LPL asp9asn (chromosome chromosome 8p22 paraoxonase 1 (PON1) PON1 met55leu and |
| 9204 | PON1 | paraoxonase 1 | PON1 | 1.8 | lipase (LPL) LPL asp9asn (chromosome chromosome 8p22 paraoxonase 1 (PON1) PON1 met55leu and paraoxonase 2 (PON2) PON2 ser311cys (chromosome chromosome 7q21.3 |
| 9205 | PON2 | paraoxonase 2 | PON2 | 1.3 | 8p22 paraoxonase 1 (PON1) PON1 met55leu and paraoxonase 2 (PON2) PON2 ser311cys (chromosome chromosome 7q21.3 tumor necrosis factor beta (TNF TNF |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | PON2 ser311cys (chromosome chromosome 7q21.3 tumor necrosis factor beta (TNF TNF beta thr26 asn (chrom chrom 6p21.3 methylenetetrahydrofolate reductase (MTHFR) MTHFR |
| 7436 | MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | MTHFR | 0.3 | TNF beta thr26 asn (chrom chrom 6p21.3 methylenetetrahydrofolate reductase (MTHFR) MTHFR 677 C/T C T (chrom chrom 1p36.3 angiotensin II receptor |
| 336 | AGTR1 | angiotensin II receptor, type 1 | AGTR1 | 0.9 | C T (chrom chrom 1p36.3 angiotensin II receptor type1 (AGTR1) AGTR1 1166 A/C A C (chromosome chromosome 3q21-25 atrial natriuretic peptide |
| 7939 | NPPA | natriuretic peptide precursor A | NPPA | 0.9 | A/C A C (chromosome chromosome 3q21-25 atrial natriuretic peptide (NPPA) NPPA 664 G/A G A (chrom chrom 1p36-21 epithelial Na channel |
| 10599 | SCNN1A | sodium channel, nonvoltage-gated 1 alpha | SCNN1A | 0.3 | G A (chrom chrom 1p36-21 epithelial Na channel subunit (SCNN1A) SCNN1A trp493arg (chromosome chromosome 12p13 FVII -232 ins/del, ins del SELE |
| 10718 | SELE | selectin E (endothelial adhesion molecule 1) | SELE | 0.6 | SCNN1A trp493arg (chromosome chromosome 12p13 FVII -232 ins/del, ins del SELE leu554phe Tumor Necrosis Factor alpha (TNFalpha) TNFalpha -376 G/A G |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNFalpha | 2.2 | ins/del, ins del SELE leu554phe Tumor Necrosis Factor alpha (TNFalpha) TNFalpha -376 G/A G A and -308 G/A G A (chromosome |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | The TNF beta thr26asn was used as further control |
| 602 | APOA4 | apolipoprotein A-IV | APOA4 | 0.3 | never selected by the five TWIST procedures apolipoprotein A4 (APOA4) APOA4 (chromosome chromosome 11q23 thr347ser apolipoprotein C3 (APOC3) APOC3 (chromosome chromosome |
| 610 | APOC3 | apolipoprotein C-III | APOC3 | 0.3 | A4 (APOA4) APOA4 (chromosome chromosome 11q23 thr347ser apolipoprotein C3 (APOC3) APOC3 (chromosome chromosome 11q23.1-q23.2 -641 C/A C A and 482 C/T; |
| 288 | ADRB3 | adrenergic, beta-3-, receptor | ADRB3 | 1.6 | and 482 C/T; C T beta 3 adrenergic receptor (ADRB3) ADRB3 trp64arg (8p12-p11.2); 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein |
| 6677 | LPL | lipoprotein lipase | LPL | 1.6 | T beta 3 adrenergic receptor (ADRB3) ADRB3 trp64arg (8p12-p11.2); 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein receptor (LDLR) LDLR (chromosome |
| 9204 | PON1 | paraoxonase 1 | PON1 | 1.8 | 3 adrenergic receptor (ADRB3) ADRB3 trp64arg (8p12-p11.2); 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein receptor (LDLR) LDLR (chromosome chromosome 19p13.3 |
| 6547 | LDLR | low density lipoprotein receptor (familial hypercholesterolemia) | LDLR | 1.8 | 8p12-p11.2 LPL ser447term PON1 gln192arg low density lipoprotein receptor (LDLR) LDLR (chromosome chromosome 19p13.3 exon 18 NcoI +/-; - cholesteryl ester |
| 1869 | CETP | cholesteryl ester transfer protein, plasma | CETP | 1.8 | exon 18 NcoI +/-; - cholesteryl ester transfer protein (CETP) CETP -631 C/A C A and -629 C/A C A (chromosome |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | NOS3 | 1.2 | C A and -629 C/A C A (chromosome chromosome 16q21 NOS3 922 A/G; A G G-protein beta 3 subunit (GNB3) GNB3 |
| 4400 | GNB3 | guanine nucleotide binding protein (G protein), beta polypeptide 3 | GNB3 | 0.3 | NOS3 922 A/G; A G G-protein beta 3 subunit (GNB3) GNB3 825 C/T C T (chromosome chromosome 12p13 beta 2 adrenergic |
| 3662 | FGB | fibrinogen beta chain | FGB | 0.3 | receptor (ADBR2) ADBR2 arg16gly (chromosome chromosome 5q31-q32 beta fibrinogen (FGB) FGB -455 G/A G A (chromosome chromosome 4q28 TNF alfa -238 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | fibrinogen (FGB) FGB -455 G/A G A (chromosome chromosome 4q28 TNF alfa -238 G/A G A and TNF beta thr26asn |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | (chromosome chromosome 4q28 TNF alfa -238 G/A G A and TNF beta thr26asn |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.2 | Besides all ALS patients were previously screened for SOD1 gene mutations with negative results thus confirming the sporadic nature |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | previously validated by ourselves 17 and others 26 and contains TNF beta as the internal control |
| 613 | APOE | apolipoprotein E | ApoE | 1.3 | Indeed ApoE arg158cys was selected by all the five TWISTs while the |
| 613 | APOE | apolipoprotein E | ApoE | 1.3 | arg158cys was selected by all the five TWISTs while the ApoE cys112arg was selected only once |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | For NOS variants the position -922 in the promoter region was never |
| 10718 | SELE | selectin E (endothelial adhesion molecule 1) | SELE | 0.6 | The two Factor VII and Selectin (SELE) SELE genetic variants both containing the information necessary for the correct |
| 10718 | SELE | selectin E (endothelial adhesion molecule 1) | SELE | 0.6 | healthy status were selected five times (FVII FVII arg353glu and SELE ser128arg and four times (FVII FVII del/ins del ins and |
| 10718 | SELE | selectin E (endothelial adhesion molecule 1) | SELE | 0.6 | ser128arg and four times (FVII FVII del/ins del ins and SELE leu554phe respectively |
| 9204 | PON1 | paraoxonase 1 | PON1 | 1.8 | paroxonase in predisposing to ALS disease appears to be confirmed PON1 met 55leu and PON2 ser311cys were chosen four times whereas |
| 9205 | PON2 | paraoxonase 2 | PON2 | 1.3 | ALS disease appears to be confirmed PON1 met 55leu and PON2 ser311cys were chosen four times whereas PON1 gln192arg was never |
| 9204 | PON1 | paraoxonase 1 | PON1 | 1.8 | met 55leu and PON2 ser311cys were chosen four times whereas PON1 gln192arg was never |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | In addition we noticed for example that in the same TNF locus 6p21.3 lies also the HFE gene for hemocromatosis and |
| 4886 | HFE | hemochromatosis | HFE | 0.5 | that in the same TNF locus 6p21.3 lies also the HFE gene for hemocromatosis and the peripherin gene both previously involved |
| 9204 | PON1 | paraoxonase 1 | PON1 | 1.8 | had already been picked up by the systems e.g for PON1 NOS and TNF |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | already been picked up by the systems e.g for PON1 NOS and TNF |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | picked up by the systems e.g for PON1 NOS and TNF |
| 602 | APOA4 | apolipoprotein A-IV | APOA4 | 0.3 | Moreover regarding APOA4 and APO C3 variants we observed that they lie on |
| 1361 | C9orf3 | chromosome 9 open reading frame 3 | APO | 0.3 | Moreover regarding APOA4 and APO C3 variants we observed that they lie on chromosome 11 |
| 613 | APOE | apolipoprotein E | ApoE | 1.3 | gene variations confirm some of the already known results (ApoE ApoE and PON for example and identify new gene/genetic gene genetic |
| 9204 | PON1 | paraoxonase 1 | PON | 1.8 | confirm some of the already known results (ApoE ApoE and PON for example and identify new gene/genetic gene genetic variations not |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | the involvement of oxidative stress as well as angiogenesis (NOS) NOS and immune response (TNF) TNF pathways |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 2.2 | as well as angiogenesis (NOS) NOS and immune response (TNF) TNF pathways |
| 6619 | LIPC | lipase, hepatic | LIPC | 0.6 | results shed light on the involvement of lipid pathways (LIPC, LIPC PPAR_amp_#x003b3 |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | this latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein e arg158cys; hepatic lipase 480 c/t; endothelial nitric oxide synthase 690 c/t and glu298asp; vitamin k dependent coagulation factor seven arg353glu glycoprotein ia/iia 873 g/a and e selectin ser128arg |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | this latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein e arg158cys; hepatic lipase 480 c/t; endothelial nitric oxide synthase 690 c/t and glu298asp; vitamin k dependent coagulation factor seven arg353glu glycoprotein ia/iia 873 g/a and e selectin ser128arg. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | the gene coding for copper/zinc superoxide dismutase 1 sod1 appears to be mutated in 10_amp_#x02013;20% in the familial form [ 1 ]. |
| 2169 | CNTF | ciliary neurotrophic factor | ciliary neurotrophic factor | 1.0 | among the genetic factors that may predispose to sporadic als neurofilaments apolipoprotein epsilon 4 genotype excitotoxicity genes ciliary neurotrophic factor ctnf cytochrome p450 debrisoquine hydroxylase cyp2d6 apurinic apyrimidinic endonuclease apex mitochondrial manganese superoxide dismutase sod2 monoamine oxidase allele b and paraoxonases have been re |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | manganese superoxide dismutase | 1.0 | filaments apolipoprotein epsilon 4 genotype excitotoxicity genes ciliary neurotrophic factor ctnf cytochrome p450 debrisoquine hydroxylase cyp2d6 apurinic apyrimidinic endonuclease apex mitochondrial manganese superoxide dismutase sod2 monoamine oxidase allele b and paraoxonases have been reported in different studies partly with contradictory results [ 2 4 7 9 ]. |
| 11609 | TBXAS1 | thromboxane A synthase 1 (platelet, cytochrome P450, family 5, subfamily A) | cytochrome p450 | 1.0 | among the genetic factors that may predispose to sporadic als neurofilaments apolipoprotein epsilon 4 genotype excitotoxicity genes ciliary neurotrophic factor ctnf cytochrome p450 debrisoquine hydroxylase cyp2d6 apurinic apyrimidinic endonuclease apex mitochondrial manganese superoxide dismutase sod2 monoamine oxidase allele b and paraoxonases have been reported in different s |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | gly adrb2 gln27glu mmp3 1171 5a/6a fii 20210 g/a fv arg506gln fvii 230 10 bp del/ins arg353glu pai 675 g5/g4 11053 g/t fgb 455 g/a itga2 873 g/a itgb3 leu33pro sele ser128arg leu554phe icam gly214arg tnf alpha 376 g/a 308g/a 244 g/a 238 g/a. |
| 7173 | MMP3 | matrix metallopeptidase 3 (stromelysin 1, progelatinase) | mmp3 | 1.0 | r 677 c/t nos3 922 a/g 690 c/t glu298asp dcp1 ivs16 ins/del agtr1 1166a/c agt met235thr nppa 664 g/a nppa 2238 t/c add1 gly460trp scnn1a trp493arg ala663thr gnb3 825 c/t adrb2 arg16gly adrb2 gln27glu mmp3 1171 5a/6a fii 20210 g/a fv arg506gln fvii 230 10 bp del/ins arg353glu pai 675 g5/g4 11053 g/t fgb 455 g/a itga2 873 g/a itgb3 leu33pro sele ser128arg leu554phe icam gly214arg tnf alpha 376 g/a 308g/ |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | genetic variants selected by the five twist procedures seven genetic variants were always independently selected by the five twist procedures: apolipoprotein e apoe chromosome 19q13.2 arg158cys; hepatic lipase lipc chromosome 15q21 23 480 c/t; endothelial nitric oxide synthase nos3 chromosome 7q36 690 c/t and glu298asp; vitamin k dependent coagulation facto |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | procedures seven genetic variants were always independently selected by the five twist procedures: apolipoprotein e apoe chromosome 19q13.2 arg158cys; hepatic lipase lipc chromosome 15q21 23 480 c/t; endothelial nitric oxide synthase nos3 chromosome 7q36 690 c/t and glu298asp; vitamin k dependent coagulation factor seven f7 chromosome 13q34 arg353glu glycoprotein ia/iia itga2 chromosome 5q23 q31 873 g/a; e selectin sele chromosom |
| 9204 | PON1 | paraoxonase 1 | paraoxonase | 1.0 | genetic variants selected four times over five experiments consisted of: peroxisome proliferator activated receptor gamma pparg pro12ala chromosome 3p25 lipoprotein lipase lpl asp9asn chromosome 8p22 paraoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensi |
| 9204 | PON1 | paraoxonase 1 | paraoxonase | 1.0 | 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin ii receptor type1 agtr1 1166 a |
| 9204 | PON1 | paraoxonase 1 | paraoxonase 1 | 1.0 | genetic variants selected four times over five experiments consisted of: peroxisome proliferator activated receptor gamma pparg pro12ala chromosome 3p25 lipoprotein lipase lpl asp9asn chromosome 8p22 paraoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin |
| 9205 | PON2 | paraoxonase 2 | paraoxonase 2 | 1.0 | imes over five experiments consisted of: peroxisome proliferator activated receptor gamma pparg pro12ala chromosome 3p25 lipoprotein lipase lpl asp9asn chromosome 8p22 paraoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin ii receptor type1 agtr1 1166 a/c |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | peroxisome proliferator activated receptor gamma | 1.0 | genetic variants independently selected by four twist procedures the number of genetic variants selected four times over five experiments consisted of: peroxisome proliferator activated receptor gamma pparg pro12ala chromosome 3p25 lipoprotein lipase lpl asp9asn chromosome 8p22 paraoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 |
| 7939 | NPPA | natriuretic peptide precursor A | atrial natriuretic peptide | 1.0 | mosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin ii receptor type1 agtr1 1166 a/c chromosome 3q21 25 atrial natriuretic peptide nppa 664 g/a chrom 1p36 21 epithelial na channel subunit scnn1a trp493arg chromosome 12p13 fvii 232 ins/del sele leu554phe tumor necrosis factor alpha tnfalpha 376 g/a and 308 g/a chromosome 6p21.3 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | receptor type1 agtr1 1166 a/c chromosome 3q21 25 atrial natriuretic peptide nppa 664 g/a chrom 1p36 21 epithelial na channel subunit scnn1a trp493arg chromosome 12p13 fvii 232 ins/del sele leu554phe tumor necrosis factor alpha tnfalpha 376 g/a and 308 g/a chromosome 6p21.3 . |
| 6709 | LTA | lymphotoxin alpha (TNF superfamily, member 1) | tumor necrosis factor beta | 1.0 | some proliferator activated receptor gamma pparg pro12ala chromosome 3p25 lipoprotein lipase lpl asp9asn chromosome 8p22 paraoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin ii receptor type1 agtr1 1166 a/c chromosome 3q21 25 atrial natriuretic peptide nppa 664 g/a |
| 7436 | MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | methylenetetrahydrofolate reductase | 1.0 | hromosome 3p25 lipoprotein lipase lpl asp9asn chromosome 8p22 paraoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin ii receptor type1 agtr1 1166 a/c chromosome 3q21 25 atrial natriuretic peptide nppa 664 g/a chrom 1p36 21 epithelial na channel subunit scnn1a trp493arg chromos |
| 6677 | LPL | lipoprotein lipase | lipoprotein lipase | 1.0 | elected by four twist procedures the number of genetic variants selected four times over five experiments consisted of: peroxisome proliferator activated receptor gamma pparg pro12ala chromosome 3p25 lipoprotein lipase lpl asp9asn chromosome 8p22 paraoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reducta |
| 336 | AGTR1 | angiotensin II receptor, type 1 | angiotensin ii receptor | 1.0 | araoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin ii receptor type1 agtr1 1166 a/c chromosome 3q21 25 atrial natriuretic peptide nppa 664 g/a chrom 1p36 21 epithelial na channel subunit scnn1a trp493arg chromosome 12p13 fvii 232 ins/del sele leu554phe tumor nec |
| 336 | AGTR1 | angiotensin II receptor, type 1 | angiotensin ii receptor type1 | 1.0 | araoxonase 1 pon1 met55leu and paraoxonase 2 pon2 ser311cys chromosome 7q21.3 tumor necrosis factor beta tnf beta thr26 asn chrom 6p21.3 methylenetetrahydrofolate reductase mthfr 677 c/t chrom 1p36.3 angiotensin ii receptor type1 agtr1 1166 a/c chromosome 3q21 25 atrial natriuretic peptide nppa 664 g/a chrom 1p36 21 epithelial na channel subunit scnn1a trp493arg chromosome 12p13 fvii 232 ins/del sele leu554phe tumor necrosis |
| 6547 | LDLR | low density lipoprotein receptor (familial hypercholesterolemia) | low density lipoprotein receptor | 1.0 | otein a4 apoa4 chromosome 11q23 thr347ser; apolipoprotein c3 apoc3 chromosome 11q23.1 q23.2 641 c/a and 482 c/t; beta 3 adrenergic receptor adrb3 trp64arg 8p12 p11.2 ; lpl ser447term; pon1 gln192arg; low density lipoprotein receptor ldlr chromosome 19p13.3 exon 18 ncoi +/ ; cholesteryl ester transfer protein cetp 631 c/a and 629 c/a chromosome 16q21 ; nos3 922 a/g; g protein beta 3 subunit gnb3 825 c/t chromosome 12p13 ; beta 2 |
| 1869 | CETP | cholesteryl ester transfer protein, plasma | cholesteryl ester transfer protein | 1.0 | me 11q23.1 q23.2 641 c/a and 482 c/t; beta 3 adrenergic receptor adrb3 trp64arg 8p12 p11.2 ; lpl ser447term; pon1 gln192arg; low density lipoprotein receptor ldlr chromosome 19p13.3 exon 18 ncoi +/ ; cholesteryl ester transfer protein cetp 631 c/a and 629 c/a chromosome 16q21 ; nos3 922 a/g; g protein beta 3 subunit gnb3 825 c/t chromosome 12p13 ; beta 2 adrenergic receptor adbr2 arg16gly chromosome 5q31 q32 ; beta fibrinogen fgb |
| 286 | ADRB2 | adrenergic, beta-2-, receptor, surface | beta 2 adrenergic receptor | 1.0 | eceptor ldlr chromosome 19p13.3 exon 18 ncoi +/ ; cholesteryl ester transfer protein cetp 631 c/a and 629 c/a chromosome 16q21 ; nos3 922 a/g; g protein beta 3 subunit gnb3 825 c/t chromosome 12p13 ; beta 2 adrenergic receptor adbr2 arg16gly chromosome 5q31 q32 ; beta fibrinogen fgb 455 g/a chromosome 4q28 ; tnf alfa 238 g/a and tnf beta thr26asn. |
| 288 | ADRB3 | adrenergic, beta-3-, receptor | beta 3 adrenergic receptor | 1.0 | owing gene/genetic variants were never selected by the five twist procedures: apolipoprotein a4 apoa4 chromosome 11q23 thr347ser; apolipoprotein c3 apoc3 chromosome 11q23.1 q23.2 641 c/a and 482 c/t; beta 3 adrenergic receptor adrb3 trp64arg 8p12 p11.2 ; lpl ser447term; pon1 gln192arg; low density lipoprotein receptor ldlr chromosome 19p13.3 exon 18 ncoi +/ ; cholesteryl ester transfer protein cetp 631 c/a and 629 c/a chro |
| 4400 | GNB3 | guanine nucleotide binding protein (G protein), beta polypeptide 3 | g protein beta 3 subunit | 1.0 | lpl ser447term; pon1 gln192arg; low density lipoprotein receptor ldlr chromosome 19p13.3 exon 18 ncoi +/ ; cholesteryl ester transfer protein cetp 631 c/a and 629 c/a chromosome 16q21 ; nos3 922 a/g; g protein beta 3 subunit gnb3 825 c/t chromosome 12p13 ; beta 2 adrenergic receptor adbr2 arg16gly chromosome 5q31 q32 ; beta fibrinogen fgb 455 g/a chromosome 4q28 ; tnf alfa 238 g/a and tnf beta thr26asn. |
| 3544 | F7 | coagulation factor VII (serum prothrombin conversion accelerator) | factor vii | 1.0 | the two factor vii and selectin sele genetic variants both containing the information necessary for the correct attribution to the disease vs healthy status were selected five times fvii arg353glu and sele ser128arg an |
| 9461 | PRPH | peripherin | peripherin | 1.0 | in addition we noticed for example that in the same tnf locus 6p21.3 lies also the hfe gene for hemocromatosis and the peripherin gene both previously involved in als disease [ 35 ]. |