Wrona Agnieszka, Widecka Krystyna, Adler Grazyna, Czekalski Stanisław, Ciechanowicz Andrzej
Samodzielna Pracownia Patobiochemii i Biologii Molekularnej Pomorskiej AM w Szczecinie.
Pol Arch Med Wewn. 2004 Feb;111(2):191-7.
The T(-344)C polymorphism in promoter of CYP11B2 gene encoding aldosterone synthase has been associated with differences in plasma aldosterone (ALDO) concentrations. In addition, the results of recent study carried out in Japan suggest that C(-344) allele of CYP11B2 may be a genetic marker of salt-sensitive hypertension characterized by low plasma renin activity (PRA) and high ALDO/PRA ratio. Therefore, it raises the question of whether the T(-344)C polymorphism of CYP11B2 gene may be associated with salt-sensitive hypertension in Caucasians. The DNA samples were obtained from 68 Polish hypertensives. During 3 subsequent 1-week periods each subject received diets of normal, low and high sodium content (120-140, 20-40 and 240-260 mmol Na+/day, respectively). Salt sensitivity was expressed as the difference between mean arterial pressure (MAP) on high salt diet and MAP on low salt one (delta MAPH-L). Genomic DNA isolated from peripheral blood nuclear cells was amplified by PCR method with primers flanking the polymorphic region and C(-344) allele was identified by gain of Hae III restriction site. There were 14 TT homozygotes (20.6%), 35 TC heterozygotes (51.5%) and 19 CC homozygotes (27.9%) in the studied group. No significant differences in delta MAPH-L, glomerular filtration rate, natriuresis, excreted fraction of filtered sodium, PRA, ALDO and ALDO/PRA ratio determined on each diet have been found in subjects according to CYP11B2 genotype. Our preliminary results suggest the lack of association of the T(-344)C CYP11B2 polymorphism with salt-sensitive hypertension as well as with activity of plasma renin-angiotensin-aldosterone system in Caucasian patients.
编码醛固酮合酶的CYP11B2基因启动子中的T(-344)C多态性与血浆醛固酮（ALDO）浓度差异有关。此外，近期在日本进行的研究结果表明，CYP11B2基因的C(-344)等位基因可能是以低血浆肾素活性（PRA）和高ALDO/PRA比值为特征的盐敏感性高血压的遗传标记。因此，这就提出了一个问题，即CYP11B2基因的T(-344)C多态性是否可能与白种人中的盐敏感性高血压有关。DNA样本取自68名波兰高血压患者。在随后连续3个为期1周的时间段内，每位受试者分别接受正常、低钠和高钠含量的饮食（分别为120 - 140、20 - 40和240 - 260 mmol Na+/天）。盐敏感性以高盐饮食时的平均动脉压（MAP）与低盐饮食时的MAP之差（δMAPH-L）表示。用位于多态性区域两侧的引物通过PCR方法扩增从外周血细胞核细胞中分离的基因组DNA，并通过获得Hae III限制性酶切位点来鉴定C(-344)等位基因。研究组中有14名TT纯合子（20.6%）、35名TC杂合子（51.5%）和19名CC纯合子（27.9%）。根据CYP11B2基因型，在受试者中未发现每种饮食条件下测定的δMAPH-L、肾小球滤过率、尿钠排泄、滤过钠排泄分数、PRA、ALDO和ALDO/PRA比值有显著差异。我们的初步结果表明，在白种人患者中，CYP11B2基因的T(-344)C多态性与盐敏感性高血压以及血浆肾素 - 血管紧张素 - 醛固酮系统的活性缺乏关联。
