A novel haplotype within C-reactive protein gene influences CRP levels and coronary heart disease risk in Northwest Indians

Mol Biol Rep. 2014 Sep;41(9):5851-62. doi: 10.1007/s11033-014-3459-0. Epub 2014 Jun 26.

Abstract

According to several epidemiological and clinical studies, the concentration of C-reactive protein (CRP) in blood is associated with the risk of coronary heart disease (CHD). However, these studies are limited in high incidence and prevalence area of North-West India. The present case control study investigated the contribution of three relevant CRP single nucleotide polymorphisms: -717A>G located in the promoter region (rs2794521), +1059G>C on exon2 (rs1800947) and +1444C>T in the 3' UTR (rs1130864) in 180 angiographically verified CHD cases and 175 control subjects. Minor allele frequencies (G, C and T) of rs2794521, rs1800947 and rs1130864 are observed to be 21.1, 11.7, 29.4 and 11.4, 10.0, 19.7 % in CHD cases and controls respectively. AA genotype of -717A>G and TT genotype of +1444C>T were significantly associated (P = 0.02 & 0.03 respectively) with the risk of CHD whereas, +1059G and +1444T were found to be strongly related (P = 0.023 & P = 0.008 respectively) with multivariable adjusted CRP levels. AGT Haplotype was significantly associated with the adjusted CRP levels (P < 0.05). Disease association analysis revealed that haplotype AGT influences CHD risk (OR 2.4, 95 % CI 1.23-4.84, P = 0.006) which exacerbates after correcting the confounding effects of risk variables (OR 2.5, 95 % CI 1.27-4.99, P = 0.004). With the global index of Akaike information criterion, it has been observed that the carrying each single unit of this susceptibility haplotype increases CHD risk by a value of 2.41 ± 0.439 (β ± SE) in the recessive mode.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / genetics*
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Coronary Disease / blood
  • Coronary Disease / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Humans
  • India
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Triglycerides / blood
  • White People / genetics*

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Triglycerides
  • C-Reactive Protein