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

J Biosci. 2011 Dec;36(5):857-68. doi: 10.1007/s12038-011-9148-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins B / genetics
  • Biomarkers / blood
  • Case-Control Studies
  • Cholesterol / blood
  • Coronary Artery Disease / genetics*
  • Female
  • Fibrinogen / genetics
  • Genetic Association Studies
  • Homocysteine / blood
  • Humans
  • India
  • Linkage Disequilibrium*
  • Male
  • Middle Aged
  • NF-kappa B / genetics
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Apolipoproteins B
  • Biomarkers
  • NF-kappa B
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Homocysteine
  • Fibrinogen
  • Cholesterol