肿瘤坏死因子受体超家族成员4（TNFRSF4）基因多态性与原发性高血压的关联

Association of TNFRSF4 gene polymorphisms with essential hypertension.

作者信息

Mashimo Yoichi, Suzuki Yoichi, Hatori Kazuko, Tabara Yasuharu, Miki Tetsuro, Tokunaga Katsushi, Katsuya Tomohiro, Ogihara Toshio, Yamada Michiko, Takahashi Norio, Makita Yoshio, Nakayama Tomohiro, Soma Masayoshi, Hirawa Nobuhito, Umemura Satoshi, Ohkubo Takayoshi, Imai Yutaka, Hata Akira

机构信息

Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.

出版信息

J Hypertens. 2008 May;26(5):902-13. doi: 10.1097/HJH.0b013e3282f6a65e.

DOI:10.1097/HJH.0b013e3282f6a65e

PMID:18398332

Abstract

BACKGROUND

Essential hypertension is a complex disorder that results from the interaction of a number of susceptibility genes and environmental factors. The TNFRSF4 (tumor necrosis factor receptor superfamily, member 4) gene was one of the genes that showed altered renal expression in long-term salt loading in mice. Moreover, association of the TNFRSF4 and TNFSF4 (tumor necrosis factor (ligand) superfamily, member 4) genes with myocardial infarction was recently reported. Since essential hypertension is a well-known risk factor for myocardial infarction, we hypothesized that TNFRSF4 could be a susceptibility gene for essential hypertension.

METHODS

We performed a case-control study of TNFRSF4 in two independent population.

RESULTS

Extensive investigation of single nucleotide polymorphisms of the entire gene suggested that it resided in one linkage disequilibrium block, and four single nucleotide polymorphisms in the 5' flanking region sufficiently represented major haplotypes. In the combined population, the frequency of the most frequent haplotype, C-C-A-A, was significantly lower (P = 8.07 x 10(-5)) and that of the second most frequent haplotype, C-T-G-A, was significantly higher (P = 6.07 x 10(-4)) in hypertensive subjects than in control subjects. This difference was observed only in female patients. The C-T-G-A haplotype showed a lower promoter activity than other haplotypes, suggesting a relationship with disease susceptibility.

CONCLUSION

Our results suggest that TNFRSF4 is a female-specific susceptible gene for essential hypertension.

摘要

背景

原发性高血压是一种复杂的疾病，由多种易感基因和环境因素相互作用导致。肿瘤坏死因子受体超家族成员4（TNFRSF4）基因是在小鼠长期盐负荷下肾脏表达发生改变的基因之一。此外，最近有报道称TNFRSF4和肿瘤坏死因子（配体）超家族成员4（TNFSF4）基因与心肌梗死有关。由于原发性高血压是心肌梗死的一个众所周知的危险因素，我们推测TNFRSF4可能是原发性高血压的一个易感基因。

方法

我们在两个独立人群中对TNFRSF4进行了病例对照研究。

结果

对整个基因的单核苷酸多态性进行广泛研究表明，它位于一个连锁不平衡区域，5'侧翼区域的四个单核苷酸多态性足以代表主要单倍型。在合并人群中，高血压患者中最常见单倍型C-C-A-A的频率显著低于对照组（P = 8.07×10⁻⁵），第二常见单倍型C-T-G-A的频率显著高于对照组（P = 6.07×10⁻⁴）。这种差异仅在女性患者中观察到。C-T-G-A单倍型的启动子活性低于其他单倍型，提示其与疾病易感性有关。