Ahmad Usman, Saleheen Danish, Bokhari Awais, Frossard Philippe M
Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, Aga Khan University, Karachi, Pakistan.
Hypertens Res. 2005 Apr;28(4):339-44. doi: 10.1291/hypres.28.339.
The objectives of this project were two-fold: to identify the genetic mutation that has been detected as an MboI dimorphism in intron 9 of the human renin (REN) gene and to confirm a previously reported, putative association between the REN MboI dimorphism and clinical diagnosis of essential hypertension (EHT) in a population of Gulf Arabs from the United Arab Emirates. Sequencing of the MboI dimorphic site was carried out on DNA of randomly chosen cases and controls. A retrospective case-control study was carried out in 689 unrelated subjects (326 first-time, clinically diagnosed hypertensives and 363 age- and gender-matched normotensive subjects), selected from the resident population of the Abu Dhabi Emirate. A polymerase chain reaction/MboI-RFLP based method was employed to compare genotype and allele distributions. Nucleotide sequences at the MboI site of the cut and uncut alleles were determined to be GATC and GGTC, respectively. This A>G mutation is located 10,631 base pairs (bp) 3' to the start of the REN gene, and 79 bp 3' to the end of exon 9. The genotype distributions of the REN 10631A>G dimorphism were found to be significantly different between hypertensive and normotensive subjects (x2= 42.29, df=2, p<0.001). Frequencies of A alleles were 0.54 in EHT vs. 0.37 in normotensive subjects, which is even more demarcated than what was found previously. The frequency of AA genotypes was higher in the hypertensive group than in the normotensive group (34.7% vs. 14.0%). The quantification of the association of A alleles with increased risk of EHT was assessed with corresponding odds ratios (OR), which gave the following values: OR of GG vs. AG genotypes, 1.3 (95% confidence interval [CI]: 0.90-1.88); OR of GG vs. AA, 3.75 (95% CI: 2.41-5.86). In conclusion, REN 10631A alleles are significantly associated with EHT in the Emirati population. This has now been found in two different and therefore independent sample populations from the Abu Dhabi Emirate. Moreover, this genetic effect seems to be acting in a recessive fashion. Hence, either the REN gene itself, or another gene that is in linkage disequilibrium with REN 10631A>G, is implicated in the pathogenesis of EHT in Emirati.
确定在人类肾素（REN）基因第9内含子中检测为MboI二态性的基因突变，并在来自阿拉伯联合酋长国的海湾阿拉伯人群体中，证实先前报道的REN MboI二态性与原发性高血压（EHT）临床诊断之间的假定关联。对随机选择的病例和对照的DNA进行MboI二态性位点测序。在从阿布扎比酋长国常住人口中选取的689名无亲缘关系的受试者（326名首次临床诊断为高血压的患者和363名年龄及性别匹配的血压正常受试者）中开展了一项回顾性病例对照研究。采用基于聚合酶链反应/MboI-RFLP的方法比较基因型和等位基因分布。切割和未切割等位基因的MboI位点的核苷酸序列分别确定为GATC和GGTC。这种A>G突变位于REN基因起始位点下游10,631个碱基对（bp）处，外显子9末端下游79 bp处。发现REN 10631A>G二态性的基因型分布在高血压患者和血压正常受试者之间存在显著差异（x2 = 42.29，自由度df = 2，p < 0.001）。EHT患者中A等位基因的频率为0.54，而血压正常受试者中为0.37，这一差异比之前发现的更为明显。高血压组中AA基因型的频率高于血压正常组（34.7%对14.0%）。用相应的优势比（OR）评估A等位基因与EHT风险增加的关联程度，结果如下：GG与AG基因型的OR为1.3（95%置信区间[CI]：0.90 - 1.88）；GG与AA基因型的OR为3.75（95% CI：2.41 - 5.86）。总之，REN 10631A等位基因与阿联酋人群中的EHT显著相关。这一结果现已在来自阿布扎比酋长国的两个不同且独立的样本群体中得到证实。此外，这种遗传效应似乎以隐性方式起作用。因此，要么是REN基因本身，要么是与REN 10631A>G处于连锁不平衡状态的另一个基因，与阿联酋人群EHT的发病机制有关。
