Rajput Charu, Makhijani Kalpana, Norboo Tsering, Afrin Farhat, Sharma Meenakshi, Pasha S Tazeen, Pasha M A Qadar
Institute of Genomics and Integrative Biology, Delhi, India.
J Hypertens. 2005 Jan;23(1):79-86. doi: 10.1097/00004872-200501000-00016.
High salt intake is the main determinant of hypertension. The alleles, which once had adaptive value in the salt-poor environment, by promoting salt retention, now induce hypertension. It would be interesting to determine whether the variant alleles of the aldosterone synthase gene (CYP11B2), if related to exaggerated expression/altered activity, are associated with hypertension when combined with a salt-rich diet.
To investigate the -344T/C, K173R and intron-2 conversion polymorphisms of CYP11B2 for an association with hypertension in highlanders accustomed to a high salt intake.
Three CYP11B2 polymorphisms were compared with respect to frequencies and clinical characteristics in 190 normotensive highlanders (NHLs) and 100 hypertensive highlanders (HHLs). One-way ANOVA, chi2 test and logistic regression analysis were carried out to investigate the association of these polymorphisms with hypertension.
The HHLs had significantly higher systolic blood pressure (SBP), diastolic blood pressure (DBP) (P < 0.0001), body mass index (BMI) (P = 0.0002), plasma aldosterone levels (P = 0.03) and aldosterone to plasma renin ratio (ARR) (P < 0.0001) and lower plasma renin activity (PRA) (P = 0.007). The -344T/C and K173R polymorphisms were in complete linkage disequilibrium with each other and the intron-2 conversion allele was in absolute association with the T allele. The TC/CC genotypes correlated with higher BMI when compared with TT genotype in the NHLs and the HHLs (P = 0.002 and 0.004, respectively). The intron-2 conversion heterozygotes/homozygotes correlated with higher SBP in the HHLs (P = 0.03) and significantly higher ARR when compared to IwIw (P = 0.02). Genotype combinations between the -344T/C and intron-2 conversion polymorphisms revealed that combinations with TC or CC genotypes inclined towards higher BMI in both the groups (P < 0.05).
Our findings showed a correlation of C allele with high BMI, suggesting that -344T/C polymorphism is in linkage disequilibrium with a functional polymorphism on the adjacent 11-beta hydroxylase gene. The correlation of the intron-2 conversion allele with high SBP and ARR associates it with hypertension. The intron-2 conversion could be a functional variant, since it has been suggested to lead to overexpression of the gene; however, the presence of another functional variant in linkage disequilibrium within the gene cannot be ruled out.
高盐摄入是高血压的主要决定因素。那些在缺盐环境中曾具有适应性价值的等位基因，通过促进盐分潴留，如今却引发了高血压。确定醛固酮合酶基因（CYP11B2）的变异等位基因若与表达过度/活性改变相关，在高盐饮食情况下是否与高血压相关，将会很有意思。
研究CYP11B2基因的-344T/C、K173R和内含子2转换多态性与习惯高盐摄入的高原人群高血压的相关性。
比较了190名血压正常的高原人群（NHLs）和100名高血压高原人群（HHLs）中三种CYP11B2多态性的频率及临床特征。采用单因素方差分析、卡方检验和逻辑回归分析来研究这些多态性与高血压的相关性。
HHLs的收缩压（SBP）、舒张压（DBP）显著更高（P<0.0001），体重指数（BMI）更高（P = 0.0002），血浆醛固酮水平更高（P = 0.03），醛固酮与血浆肾素比值（ARR）更高（P<0.0001），而血浆肾素活性（PRA）更低（P = 0.007）。-344T/C和K173R多态性彼此处于完全连锁不平衡状态，内含子2转换等位基因与T等位基因完全相关。在NHLs和HHLs中，与TT基因型相比，TC/CC基因型与更高的BMI相关（分别为P = 0.002和0.004）。内含子2转换杂合子/纯合子与HHLs中更高的SBP相关（P = 0.03），与IwIw相比，ARR显著更高（P = 0.02）。-344T/C和内含子2转换多态性之间的基因型组合显示，两种人群中TC或CC基因型组合倾向于更高的BMI（P<0.05）。
我们的研究结果显示C等位基因与高BMI相关，表明-344T/C多态性与相邻的11-β羟化酶基因上的一个功能性多态性处于连锁不平衡状态。内含子2转换等位基因与高SBP和ARR的相关性使其与高血压相关。内含子2转换可能是一个功能性变异，因为有人认为它会导致该基因的过表达；然而，不能排除该基因内存在处于连锁不平衡状态的另一个功能性变异。
Zotero 插件