Tanaka Chihiro, Mannami Toshifumi, Kamide Kei, Takiuchi Shin, Kokubo Yoshihiro, Katsuya Tomohiro, Kawano Yuhei, Miyata Toshiyuki, Ogihara Toshio, Tomoike Hitonobu
Research Institute, National Cardiovascular Center, Suita, Japan.
Hypertens Res. 2005 Jan;28(1):35-41. doi: 10.1291/hypres.28.35.
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.
众所周知，血浆中炎症标志物如白细胞介素-6（IL-6）水平升高与动脉粥样硬化和心肌梗死有关。本研究的目的是揭示IL-6基因单核苷酸多态性（SNP）对日本普通人群血压调节和动脉粥样硬化进展的影响。为了评估IL-6基因遗传变异的潜在影响，我们通过直接测序对IL-6基因的整个编码区和启动子区进行了8个SNP的探索，并对2421名日本受试者（1162名男性和1259名女性）的启动子区-636G>C和内含子3中的1691C>G这两个SNP进行了基因分型。结果显示，在调整所有混杂因素后，-636 G>C与女性的收缩压（SBP）和颈动脉内膜中层厚度（IMT）显著相关，1691C>G与男性的SBP和颈动脉IMT相关。虽然这两个SNP与高血压患病率均无显著相关性，但单倍型频率分析表明，在-636和1691位点均携带G等位基因的高血压男性数量显著多于具有这种组合的非高血压男性。因此，IL-6基因启动子区和内含子3中的这两个SNP可能在日本人的血压调节和动脉粥样硬化进展中发挥作用。
