Title: Genetic Markers of CHD Risk in Men and Women
Principal Investigator: Richard Donahue, PhD, MPH
Funding Agency: NIH/NHLBI
Period: 08/01/04 - 07/31/09
Abstract: We propose to determine whether the variability in several genes that influence inflammation and endothelial dysfunction are related to the odds of MI among 700 men and 229 postmenopausal women from the Western New York Health Study.
We will examine the following specific aims:
1) We hypothesize that cases of acute MI will have a higher frequency of specific haplotypes at the C-reactive protein locus composed of alleles associated with higher levels of CRP production (-732G/A), 1059G/C, and +1444C/T) than matched controls. MI cases will have a greater frequency of haplotypes composed of alleles associated with higher levels of IL-6 production (-597G/A, -572G/C, and -174G/C) than controls, and a lower frequency of specific haplotypes in the IL1A/IL1B/IL1RN gene region;
2) cases will have a higher frequency of alleles and haplotypes for specific functional polymorphisms of the E-selectin gene (S128R and G98T) than controls;
3) to utilize DNA pooling strategy for rapid screening of large numbers of single nucleotide polymorphisms (SNPs) in 29 candidate genes in relevant biological pathways and test selected loci for association with risk of acute MI;
4) for those loci with evidence of association, to identify haplotype tagging SNPs (htSNPs) that capture the variation at each locus and test for association between these SNPs and haplotypes and risk of MI. Secondary aims will a) explore the above associations among men with premature MI (55 years of age or less) and b) explore gene- gene and gene- environment interactions. MI case subjects were identified from hospital record review in Erie and Niagara counties (95% of all eligible cases, ICD9 410-410.9) an average of 4 months post MI. They were interviewed and examined in 1996-2001. Control subjects were randomly selected from the same counties (59.5% response rate) and had a contemporaneous clinical exam. Controls will be individually matched to cases by age, sex, and ethnicity. This innovative and cost-efficient method may yield new insights into the genetic risks underlying acute MI.