Ramanathan Gnanasambandan, Elumalai Ramprasad, Periyasamy Soundararajan, Lakkakula Bhaskar V K S
Department of Biomedical Sciences, Sri Ramachandra University, Chennai, Tamil Nadu, India.
Department of Nephrology, Sri Ramachandra University, Chennai, Tamil Nadu, India.
Saudi J Kidney Dis Transpl. 2017 May-Jun;28(3):552-557. doi: 10.4103/1319-2442.206464.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD) and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544) were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.
常染色体显性多囊肾病（ADPKD）是最常见的遗传性肾病，其特征为双侧肾囊肿。高血压是ADPKD患者慢性肾病（CKD）和死亡的常见原因。肾素 - 血管紧张素 - 醛固酮系统的醛固酮合酶基因多态性作为高血压候选基因已得到广泛研究。本研究旨在探讨CYP11B2基因对ADPKD患者CKD进展的潜在修饰作用。根据Ravine纳入和排除标准招募了102例ADPKD患者和106例健康对照。使用基于荧光共振能量转移（FRET）的竞争性等位基因特异性PCR（KASPar）方法对CYP11B2基因内的三个标签单核苷酸多态性（rs3802230、rs4543和rs4544）进行基因分型。采用 Cochr an - Armitage趋势检验评估这些多态性与CKD分期之间的潜在关联。使用Mantel - Haenszel分层分析来探讨这些多态性的混杂和交互作用。在所基因分型的三个标签单核苷酸多态性中，rs4544多态性呈单态性且rs3802230偏离哈迪 - 温伯格平衡。CYP组11B2标签单核苷酸多态性与ADPKD或CKD无显著关联。此外，这些多态性对CKD进展与高血压之间的关系未表现出混杂作用。我们的结果表明，醛固酮合酶基因不是南印度ADPKD患者CKD进展的主要易感基因。
