Association of TNFRSF4 gene polymorphisms with essential hypertension
Association of TNFRSF4 gene polymorphisms with essential hypertension
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DOI：
10.1097/hjh.0b013e3282f6a65e
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发表时间：
2008-05-01
影响因子：
4.9
通讯作者：
Hata, Akira
中科院分区：
文献类型：
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作者：
Mashimo, Yoichi;Suzuki, Yoichi;Hata, Akira
背景原发性高血压是一种由多种易感基因和环境因素共同作用的复杂疾病。TNFRSF 4（肿瘤坏死因子受体超家族，成员4）基因是在小鼠长期盐负荷中显示改变的肾表达的基因之一。此外，最近报道了TNFRSF 4和TNFSF 4（肿瘤坏死因子（配体）超家族，成员4）基因与心肌梗死的关联。由于原发性高血压是心肌梗死的危险因素，我们假设TNFRSF 4可能是原发性高血压的易感基因，方法在两个独立的人群中进行TNFRSF 4的病例对照研究。在50个侧翼区域中的4个单核苷酸多态性充分代表了主要的单倍型。在合并人群中，高血压患者中最常见的单倍型C-C-A-A的频率显著低于对照组（P = 8.07 × 10（-5）），第二常见的单倍型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。结论TNFRSF 4是原发性高血压女性特异性易感基因。
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 50 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.