A single nucleotide polymorphism in the gene encoding fibrinogen beta chain is associated with hypertension

Abstract

Introduction: Fibrinogen, a major determinant of blood viscosity, is an acute phase protein associated with cardiovascular disease. We studied the association of hypertension with single nucleotide polymorphisms (SNPs) in the gene encoding fibrinogen beta chain (FGB). Methods: Three tagging SNPs (rs1025154, rs4220 and rs1044291) were selected from the HapMap database on Han Chinese. Genotypes were determined in 1375 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. There were 210 and 372 hypertensive subjects at baseline and at the six-year follow-up, respectively. Results: Among the 3 SNPs, rs4220 showed an association with hypertension at baseline (OR¼ 1.49, P ¼ 0.004) and at follow-up (OR¼ 1.28, P ¼ 0.024), after adjusting for age, sex, current smoking, drinking and education. This SNP was associated with higher plasma fibrinogen level (b¼ 0.15, Po0.001 at baseline and b¼ 0.13, Po0.001 at follow-up). The association with hypertension remains significant after further adjusting for body mass index and fibrinogen level (OR¼ 1.43, P ¼ 0.014 at baseline; OR¼ 1.29, P¼ 0.038 at follow-up). Conclusion: The SNP rs4220 in FGB, which leads to substitution of arginine by lysine at position 448, is associated with plasma fibrinogen level and hypertension independently in Hong Kong Chinese. This suggests that fibrinogen may be causally linked to hypertension, directly or indirectly, and that elevated fibrinogen level in hypertension is not merely a consequence of elevated blood pressure.