ABCA1 p.Gly455Ala
| Predicted by SNAP2: | A: N (72%), C: D (59%), D: N (61%), E: N (78%), F: D (71%), H: N (57%), I: N (66%), K: N (57%), L: N (53%), M: N (57%), N: N (93%), P: N (61%), Q: N (78%), R: N (61%), S: N (82%), T: N (66%), V: N (57%), W: D (75%), Y: D (71%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Candidate gene susceptibility variants predict int... Am Heart J. 2005 Aug;150(2):243-50. Whiting BM, Anderson JL, Muhlestein JB, Horne BD, Bair TL, Pearson RR, Carlquist JF
Candidate gene susceptibility variants predict intermediate end points but not angiographic coronary artery disease.
Am Heart J. 2005 Aug;150(2):243-50., [PMID:16086925]
Abstract [show]
BACKGROUND: Moderate-sized studies have suggested that variants of candidate genes can influence laboratory markers of coronary artery disease (CAD), but whether they predict parallel changes in clinical CAD risk is unknown. METHODS: We studied a single nucleotide polymorphism (SNP) from each of the 5 candidate genes for intermediate (laboratory) and clinical (angiographic CAD) end points in a large cohort of patients. The 5 gene SNPs were cholesteryl ester transfer protein (CETP) TaqIB (N = 3219), ATP-binding cassette (ABCA1) G596A (N = 3302), lipoprotein lipase (LPL) HindIII (N = 909), plasminogen activator inhibitor, type 1 (PAI1), 4G/5G (N = 1142), and hepatic lipase (HL) C-541T (N = 4704). Intermediate outcomes were high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). Cases had 1- to 3-vessel CAD (> or = 70% stenosis); controls had angiographically normal coronaries. RESULTS: Cholesteryl ester transfer protein predicted HDL (mean, B1B1 35.0 mg/dL, B2B2 38.6 mg/dL; P < .001) but not CAD (B1B1 74%, B2B2 70%; adjusted P = .35, odds ratio [OR] = 0.89). ABCA1 predicted HDL (mean, GG = 36.4 mg/dL, AA = 39.2 mg/dL; P = .02) but not CAD (GG 74%, AA 75%; adjusted P = .96, OR = 0.99). HL predicted HDL (CC 37.1 mg/dL, TT 40.9 mg/dL; P = .002) but not CAD (CC 71%, TT 68%, adjusted P = .66, OR = 0.94). LPL predicted TG (median: [++] 134, [--] 98 mg/dL; P < .001) but not CAD ([++] 79%, [--] 79%; adjusted P = .99, OR = 1.00). PAI1 predicted TG (median, 4G4G 130 mg/dL, 5G5G 148 mg/dL; P = .16), but not CAD (4G4G 77%, 5G5G 76%; adjusted P = .62, OR = 1.11). CONCLUSIONS: Five SNPs predicted differences in risk-related lipids but not angiographic CAD. These discrepancies suggest that genetic determinants of CAD are complex and intermediate phenotypes are poor surrogates. These findings have important implications for future directions in genetic research.
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No. Sentence Comment
113 The G455A polymorphism of the h-fibrinogen gene consistently correlates with elevated plasma fibrinogen,37 a known predictor of cardiovascular disease.38 However, the large ECTIM study found no relation between genotype and clinical outcomes although an association with severity of coronary heart disease was reported.37,39 A thermolabile variant of methylenetetrahydrofolate reductase is associated with increased accumulation of the toxic amino acid homocysteine, but despite initial reports, it has weak, if not absent, association with cardiovascular outcomes.40-42 Mechanistic considerations The explanation for widespread discrepancies between changes in intermediate phenotypes and clinical outcomes associated with genetic variants is uncertain and will require substantial future research efforts.
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ABCA1 p.Gly455Ala 16086925:113:4
status: NEW