Tripathi Gaurav, Dharmani Poonam, Khan Faisal, Sharma R K, Pandirikkal Vinod, Agrawal Suraksha
Department of Medical Genetics, Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow (UP) 226014, India.
BMC Nephrol. 2006 Oct 17;7:15. doi: 10.1186/1471-2369-7-15.
The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1) is an important component of RAS which determines the vasoactive peptide Angiotensin-II.
In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8) and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease determined from the serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain reaction (PCR) based DNA amplification using specific flanking primers Based on the method described elsewhere.
The difference of DD and II genotypes was found highly significant among the two groups (p = 0.025; OR = 3.524; 95% CI = 1.54-8.07). The combined genotype DD v/s ID+II comparison validated that DD genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95% CI limit = 3.4-8.5). However, no correlation was obtained for different biochemical parameters of lipid profile and renal function among DD and non DD genotype. Interestingly, approximately 87% of the DD ESRD patients were found hypertensive in comparison to the 65% patients of non DD genotype
Based on these observations we conclude that ACE DD genotype implicate a strong possible role in the hypertensive state and in renal damage among north Indians. The study will help in predetermining the timing, type and doses of anti-hypertensive therapy for ESRD patients.
肾素 - 血管紧张素系统（RAS）是血压和肾脏功能及其相互作用的关键调节因子。在这种情况下，RAS不同组分基因的遗传变异性可能导致其在肾病患者中的异质性关联。血管紧张素转换酶 - 1（ACE - 1）是RAS的重要组成部分，它决定血管活性肽血管紧张素 - II。
在本研究中，我们调查了来自印度北部的127例终末期肾病（ESRD）患者和150名正常健康对照者，以推断ACE基因多态性与ESRD之间的关联。患者的纳入标准包括血清肌酐水平持续高于正常范围（3.4至15.8），并且这些患者被推荐进行肾移植。总共150名正常健康对照者也进行了ACE I/D多态性基因分型。将对照样本定义为正常的标准完全基于血清肌酐水平确定的无任何肾脏疾病。ACE I/D基因分型通过基于聚合酶链反应（PCR）的DNA扩增，使用特定侧翼引物进行检测，方法基于其他地方描述的方法。
发现两组之间DD和II基因型的差异非常显著（p = 0.025；OR = 3.524；95％CI = 1.54 - 8.07）。DD基因型与ID + II基因型的联合比较证实，DD基因型是ESRD的高风险基因型（p = 0.001；OR = 5.74；95％CI范围 = 3.4 - 8.5）。然而，DD和非DD基因型之间脂质谱和肾功能的不同生化参数未获得相关性。有趣的是，与65％的非DD基因型患者相比，约87％的DD基因型ESRD患者患有高血压。
基于这些观察结果，我们得出结论，ACE DD基因型在印度北部人群的高血压状态和肾脏损伤中可能起着重要作用。该研究将有助于预先确定ESRD患者抗高血压治疗的时间、类型和剂量。
