Single Nucleotide Polymorphisms in the Interleukin-6 Gene Associated with Blood Pressure and Atherosclerosis in a Japanese General Population

It is known that increased plasma levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with atherosclerosis and myocardial infarction. The aim of this study was to reveal the contribution of the single nucleotide polymorphisms (SNPs) of the IL-6 gene on the blood pressure regulation and progression of atherosclerosis in a general Japanese population. In order to evaluate the potential implications of genetic variability of the IL-6 gene, we explored eight SNPs by direct sequencing for the entire coding region and the promoter region in the IL-6 gene and genotyped two SNPs, −636G>C in the promoter region and 1691C>G in intron 3, for a total of 2,421 Japanese subjects (1,162 men and 1,259 women). As a consequence, −636 G>C was significantly associated with systolic blood pressure (SBP) and carotid intima-media thickness (IMT) in women, and 1691C>G showed a relationship with SBP and carotid IMT in men after adjustment for all confounding factors. Although neither SNP had a significant correlation to the prevalence of hypertension, the haplotype frequency analysis indicated that the number of hypertensive men with a G allele at both −636 and 1691 was significantly greater than the number of nonhypertensive men with this combination. Thus, these two SNPs in the promoter region and intron 3 of the IL-6 gene might play a role in the blood pressure regulation and progression of atherosclerosis in the Japanese.