title: A two-step genetic study on quantitative precursors of coronary artery disease in a homogeneous Indian population: case-control association discovery and validation by transmission-disequilibrium test.
abstract: In spite of its strong familiality, gene identification for coronary artery disease (CAD) has not yielded a consistent picture. One major reason for this is that families or cases and controls were not recruited from a homogeneous population. We, therefore, attempted to map genes underlying 10 quantitative traits (QTs) that are known precursors of CAD in a homogeneous population (Marwari) of India. The QTs are apolipoprotein B (ApoB), C-reactive protein (CRP), fibrinogen (FBG), homocysteine (HCY), lipoprotein (a) (LPA), cholesterol - total (CHOL-T), cholesterol - HDL (CHOL-H), cholesterol - LDL (CHOL-L), cholesterol - VLDL (CHOL-V) and triglyceride (TG). We assayed 209 SNPs in 31 genes among members of Marwari families. After log-transformation and covariate-adjustment of the QTs, a two-step analysis was performed. In Step-1, data on unrelated individuals were analysed for association with the SNPs. In Step-2, for validation of Step-1 results, a quantitative transmission-disequilibrium test on parent- offspring data was performed for each SNP found to be significantly associated with a QT in Step-1 on an independent sample set drawn from the same population. Statistically significant results found for the various QTs and SNPs were: rs3774933, rs230528, rs230521, rs1005819 and rs1609798 (intronic, NFKB1) with APOB; rs5361 (Missense, R greatr than S, SELE) and rs4648004 (Intronic, NFKB1) with FBG; rs4220 (Missense, K greater than R, FGB) with HCY; and rs3025035 (Intronic, VEGFA) with CHOL-H. SNPs in SELE, VEGFA, FGB and NFKB1 genes impact significantly on levels of quantitative precursors of CAD in Marwaris.
authors: Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
authors: Sanjukta
authors: S
authors: Mallik
authors: Partha P
authors: PP
authors: Majumder
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D056726:Genetic Association Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; D015415:Biomarkers; D016328:NF-kappa B; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006710:Homocysteine; D005340:Fibrinogen; D002784:Cholesterol