Ramanathan Gnanasambandan, Ghosh Santu, Elumalai Ramprasad, Periyasamy Soundararajan, Lakkakula Bhaskar V K S
Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India.
Department of Environmental Health Engineering, Sri Ramachandra University, Chennai, India.
Indian J Med Res. 2016 Jun;143(6):748-755. doi: 10.4103/0971-5916.191992.
BACKGROUND & OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. m0 ethods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction.
All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD.
INTERPRETATION & CONCLUSIONS: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.
常染色体显性多囊肾病（ADPKD）是一种遗传性全身性疾病，其特征是肾脏中充满液体的囊肿，在晚年可导致终末期肾衰竭。高血压是导致慢性肾脏病（CKD）进展的主要独立因素之一。肾素 - 血管紧张素 - 醛固酮系统（RAAS）基因作为高血压候选基因已被广泛研究。本研究的目的是探讨血管紧张素转换酶标签单核苷酸多态性（ACE标签-SNP）在ADPKD患者CKD进展中的作用。方法：本研究调查了102例ADPKD患者和106例对照者中的6个ACE标签SNP（血管紧张素转换酶标签单核苷酸多态性）以及插入/缺失（I/D）情况。使用基于荧光共振能量转移的KASPar方法对标签SNP进行基因分型，通过聚合酶链反应（PCR）和电泳对ACE I/D进行检测。比较了ADPKD患者和对照者的基因型和单倍型。进行单因素和多因素逻辑回归分析以评估基因型和高血压对CKD进展的影响。采用Mantel-Haenszel（M-H）分层分析研究不同CKD阶段与高血压及其相互作用之间的关系。结果：所有位点均具有多态性，除rs4293 SNP外，其余位点均符合Hardy-Weinberg平衡。对照者和ADPKD患者中ACE基因型和单倍型的分布无显著差异。在形成两个连锁不平衡（LD）块的SNP之间观察到显著的连锁不平衡。单因素分析显示，年龄、高血压、糖尿病家族史和ACE rs4362与CKD进展有关。解读与结论：结果表明，ACE基因型是ADPKD患者中高血压与CKD进展关系的效应修饰因子。
