Eguchi Takashi, Maruyama Tatsuya, Ohno Yoichi, Morii Toshiyuki, Hirao Keiichi, Hirose Hiroshi, Kawabe Hiroshi, Saito Ikuo, Hayashi Matsuhiko, Saruta Takao
Department of Internal Medicine, School of Medicine, Keio University, Saitama Prefecture, Japan.
Hypertens Res. 2009 Sep;32(9):775-9. doi: 10.1038/hr.2009.91. Epub 2009 Jun 26.
The tumor necrosis factor (TNF)-alpha pathway has a key role in regulating insulin resistance. TNF receptor 2 (TNFR2) is an emerging candidate gene for insulin resistance in essential hypertension. We examined the association of insulin resistance and enhanced TNF pathway with severe hypertension and the association of a microsatellite polymorphism of the TNFR2 gene with severe hypertension. Male severe essential hypertensive patients (HT) with the onset before 60 years of age and with genetic predispositions to hypertension were consecutively enrolled at our outpatient department (N=92). Normotensive men (NT) over 50 years of age were randomly registered from the participants in the annual health check program (N=78). Patients were selected as HT and NT who met stringent criteria for systolic/diastolic blood pressure (SBP/DBP) levels >or=180 and/or 110 mm Hg and <120/80 mm Hg, respectively. HT revealed significantly higher plasma insulin levels, C-reactive protein (CRP) and soluble fraction of TNFR2 concentrations (sTNFR2) than NT. A microsatellite polymorphism of the CA repeat in intron 4 of the TNFR2 gene was analyzed. The allele frequency of CA16 in HT differed significantly from that in NT (66/184 vs. 36/156, P=0.01 by chi(2) analysis). In HT, the CA16 carriers showed significantly higher SBP and plasma insulin levels and a higher tendency of sTNFR2 than did those without this allele. In NT, CA16 carriers revealed significantly higher sTNFR2 and CRP levels than did the CA16 non-carriers. These results suggest that the TNFR2 gene locus has a potential effect on developing severe hypertension through the augmented TNF pathway and insulin resistance.
肿瘤坏死因子（TNF）-α通路在调节胰岛素抵抗中起关键作用。肿瘤坏死因子受体2（TNFR2）是原发性高血压中胰岛素抵抗的一个新兴候选基因。我们研究了胰岛素抵抗和增强的TNF通路与重度高血压的关联，以及TNFR2基因微卫星多态性与重度高血压的关联。连续纳入我院门诊60岁以前发病且有高血压遗传易感性的男性重度原发性高血压患者（HT，n = 92）。从年度健康体检项目参与者中随机选取年龄超过50岁的血压正常男性（NT，n = 78）。分别将收缩压/舒张压（SBP/DBP）水平≥180和/或110 mmHg以及＜120/80 mmHg的患者选为HT和NT。HT患者的血浆胰岛素水平、C反应蛋白（CRP）和TNFR2可溶性部分浓度（sTNFR2）显著高于NT患者。分析了TNFR2基因第4内含子中CA重复序列的微卫星多态性。HT患者中CA16的等位基因频率与NT患者有显著差异（66/184 vs. 36/156，χ²分析，P = 0.01）。在HT患者中，CA16携带者的SBP和血浆胰岛素水平显著更高，sTNFR2水平也有更高的趋势，而无该等位基因者则不然。在NT患者中，CA16携带者的sTNFR2和CRP水平显著高于非携带者。这些结果表明，TNFR2基因位点可能通过增强的TNF通路和胰岛素抵抗对重度高血压的发生发展产生潜在影响。
