Firouzi Mehran, Kok Bart, Spiering Wilko, Busjahn Andreas, Bezzina Connie R, Ruijter Jan M, Koeleman Bobby P C, Schipper Maria, Groenewegen W Antoinette, Jongsma Habo J, de Leeuw Peter W
Department of Medical Physiology, University Medical Center, Utrecht, The Netherlands.
J Hypertens. 2006 Feb;24(2):325-30. doi: 10.1097/01.hjh.0000200512.40818.47.
Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examined the hypothesis that these polymorphic variants are associated with hypertension and that they interact with blood pressure in healthy individuals.
Cx40 genotypes were determined in 191 subjects with essential hypertension, 198 normotensive individuals, and a healthy control population (178 twin pairs, 108 monozygotic, 70 dizygotic).
We found a significant contribution of the minor Cx40 allele or genotype (-44AA/+71GG) to the risk of hypertension in men (P = 0.013 or P = 0.035; odds ratio, 1.87 or 2.10, respectively), but not in women. Moreover, in the healthy control population a significant effect of Cx40 genotype and sex on systolic blood pressure was found (P < 0.05 and P < 0.0001, respectively). Women carrying the minor Cx40 genotype had significantly higher systolic blood pressure compared with non-carriers (P < 0.05). In men, systolic blood pressure in carriers of the minor Cx40 genotype was not significantly different from the other two genotypes, possibly because of the small number of men in this group. However, men carrying the -44GA/+71AG genotype had higher standing systolic blood pressure compared with the more common Cx40 genotype (-44GG; P = 0.033).
These findings suggest that the Cx40 polymorphisms may form a genetic susceptibility factor for essential hypertension in men.
由连接蛋白（Cx）形成的缝隙连接在血管张力调节中起重要作用。此前，我们报道了血管壁和肾脏中主要连接蛋白Cx40基因调控区域内两个紧密连锁的多态性位点（-44G→A和+71A→G）。在本研究中，我们检验了以下假设：这些多态性变体与高血压相关，且它们在健康个体中与血压相互作用。
在191例原发性高血压患者、198例血压正常个体以及一个健康对照人群（178对双胞胎，108对同卵双胞胎，70对异卵双胞胎）中确定Cx40基因型。
我们发现Cx40次要等位基因或基因型（-44AA/+71GG）对男性患高血压风险有显著影响（P = 0.013或P = 0.035；优势比分别为1.87或2.10），但对女性无此影响。此外，在健康对照人群中，发现Cx40基因型和性别对收缩压有显著影响（分别为P < 0.05和P < 0.0001）。携带Cx40次要基因型的女性与非携带者相比，收缩压显著更高（P < 关于Cx40次要基因型携带者的男性，收缩压与其他两种基因型相比无显著差异，可能是因为该组男性数量较少。然而，携带-44GA/+71AG基因型的男性与更常见的Cx40基因型（-44GG）相比，站立时收缩压更高（P = 0.033）。
这些发现表明，Cx40多态性可能是男性原发性高血压的一个遗传易感性因素。
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