The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype

Diab Vasc Dis Res. 2007 Jun;4(2):124-9. doi: 10.3132/dvdr.2007.030.

Abstract

The present study investigated genetic variation in the 3' flanking region of ApoA-I (PstI), the 3' untranslated region of ApoC-III (SstI) and intron 2 of ApoA-IV (XbaI) in 435 type 2 diabetes mellitus patients, divided according to the presence or absence of coronary heart disease (CHD). Uncommon allele frequencies (P2, S2, X2) were 17.5%, 32.5%, 16.2% and 29.5%, 17.9%, 13.8% in patients with and without CHD, respectively. Linkage disequilibrium (D' = 0.31-0.73, p<0.01) was observed in all diallelic pairs except XbaI/PstI and XbaI/SstI in patients having CHD. Haplotype analysis revealed that P1-S2-X1 is a susceptibility haplotype that increases the risk of CHD in diabetes (OR 2.85, CI 1.51-5.61), exacerbating risk (OR 3.57, CI 1.81-7.45) even after adjustment for confounders. The findings in the present study suggest that each unit of P1-S2-X1 in diabetes increases the risk of CHD by a factor of 1.37+/-0.307 (beta + SE), which is manifest in its multiplicative mode.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Flanking Region
  • 3' Untranslated Regions
  • Adult
  • Aged
  • Apolipoprotein A-I / genetics*
  • Apolipoprotein C-III / genetics*
  • Apolipoproteins A / genetics*
  • Coronary Disease / blood
  • Coronary Disease / genetics*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Humans
  • India
  • Introns
  • Linkage Disequilibrium
  • Lipids / blood*
  • Male
  • Middle Aged
  • Multigene Family*
  • Odds Ratio
  • Polymorphism, Restriction Fragment Length
  • Risk Assessment
  • Risk Factors

Substances

  • 3' Untranslated Regions
  • Apolipoprotein A-I
  • Apolipoprotein C-III
  • Apolipoproteins A
  • Lipids
  • apolipoprotein A-IV