Association of fibrinogen alpha-chain polymorphisms with coronary atherosclerosis and plasma fibrinogen concentration

OBJECTIVE To identify genetic susceptibility to coronary artery disease (CAD), associated with fibrinogen a-chain (FGA) single nucleotide polymorphisms (SNPs). METHOD A prospective, genetic association study was performed in 106 inpatients undergoing coronary angiography, comprising 77 cases of documented CAD and 29 control subjects free of CAD. Gensini score was calculated to assess CAD severity. Blood fibrinogen concentration was measured in all subjects. Genotyping for FGA SNPs rs2070022 C/T, rs2070016 C/T and rs2070006 A/G was performed. RESULTS The incidence of rs2070022 CC and rs2070006 AG/GG genotypes was higher in cases with CAD than in control subjects (86.7% vs 61.9%, p=0.027 and 91.4% vs 75.9%, p=0.043, respectively). A significant effect of the same genotypes upon CAD occurrence was observed (OR=4; p=0.027, OR=3.394; p=0.045, respectively). Subjects with rs2070022 CC genotype had higher plasma fibrinogen concentration than carriers of CT/TT alleles (430.15 +/- 21.96 mg/dL vs 354.64 +/- 30.22 mg/dL, p=0.05). Subjects with rs2070016 CT/TT alleles had elevated fibrinogen concentrations, compared to homozygotes for CC genotype (417.98 +/- 19.29 mg/dL vs 307 +/- 15 mg/dL, p=0.003). Homozygotes for rs2070016 CC genotype had a higher Gensini score than carriers of CT and TT alleles (46.67 +/- 37.11 vs 24.64 +/- 3.69, p=0.015). CONCLUSIONS FGA SNPs were related to significant coronary atherosclerosis (rs2070022 CC, rs2070006 AG/GG), plasma fibrinogen concentration (rs2070022 CC, rs2070016 CT/TT) and Gensini score (rs2070016 CC).