Interleukin-6 gene -573G>C promoter polymorphism is associated with plasma fibrinogen level and hypertension in Hong Kong Chinese

Abstract

Inflammation is an important mechanism in cardiovascular disease. Interleukin-6 (IL-6) is the major regulator of acute phase protein synthesis1 and plays important roles in the pathogenesis of cardiovascular disorders. Elevated IL-6 levels are associated with the development and severity of coronary disease as well as the transition to plaque instability and subsequent poor outcome in atherosclerotic processes. Several single nucleotide polymorphisms (SNPs) in the IL-6 gene promoter have been reported, of which the -174G>C has been shown to influence the basal level of circulating IL-6 in vivo and endothelial function in healthy subjects. We sought to study IL-6 gene promoter polymorphisms in the Hong Kong Chinese and determined their association with hypertension and plasma fibrinogen levels. SNPs in the IL-6 gene promoter was identified by direct sequencing of a 945-bp segment of the 5′-flanking region of IL-6 gene in which most known SNPs are located in 40 Hong Kong Chinese subjects [20 subjects with a history of ischemic heart disease (IHD) or stroke, and 20 normal controls]. Large-scale screenings of the identified SNPs were performed in 111 essential hypertensives and 118 sex and age-matched normotensive controls, using the Sequenom genotyping platform. Plasma levels of acute phase proteins were determined. A major SNP: -573C>G (rs1800796) polymorphism was found in our population (-573G allele frequency 0.24). The genotypes of -573C>G polymorphism were in Hardy-Weinberg equilibrium (p=0.92). The -174G>C and -598G>A polymorphisms, which are present in Caucasians, were almost 100% homozygous in our population. Subjects with -573G allele (CG+GG genotypes) had a higher blood level of fibrinogen than with CC (3.12±0.05 vs. 2.92±0.06, p=0.018). The -573G allele was also found to be associated with hypertension (P=0.047). In conclusion, our results raise the possibility that IL-6 gene might play a role in the pathogenesis of hypertension.