Abstract 4883: Genome Wide Analyses Reveal a X-Chromosomal Single Nucleotide Polmorphism as Risk Factor for Coronary Artery Disease in Men
Objective: In an effort to detect gene variations relevant for coronary artery disease (CAD), DNA samples of the AtheroGene study, a case-control study including cases of doctumented CAD, were genotyped to target non-synonymous single nucleotide polymorphisms (SNPs) in approx. 20.000 genes.
Methods: DNA samples of patients with documented CAD of the AtheroGene study (n = 697, 346 cases and 351 controls) were genotyped using the Affymetrix human 20K cSNP panel and the universal 25K Tag Array. Results of this genome-wide scan were validated in CAD cases and matched controls of the PRIME study (n = 696, 295 cases and 301 controls) using the same Affymetrix technology. Selected SNPs were further replicated in multiple independent cohorts (ECTIM, PRIME2, complete AtheroGene study and AFIJI, in total n= 3718) by the 5′ nuclease assay and combined meta-analysis was used for statistical analysis.
Results: Genetic analyses revealed a strong associateion of the non-synonymous polymorphism rs1190736 (A/C) with early coronary artery diseasein men but not in women (meta- analysis men: OR 1.37 (95% CI: 1.21–1.56, p-value 1.0×10−6); women: OR 1.00 (95% CI: 0.81–1.24, p-value 0.967). The SNP rs 1190736 is located within the exon 1 of the GPR101 gene, located on the x chromosomme and introduces an amino acid exchange at position 124 of the protein (Leucin to Valin). GPR101 encodes a G-protein coupled receptor with so far unknown function.
Conclusion: In conclusion, the X- chromosomal single nucleotide polymorphism rs1190736 is strongly associated with coronary artery disease only in men and increases the risk of incident coronary artery disease in men. This SNP has been identifed as top ranked using the 20K non synonymous cSNP panel.