Angiotensin-Converting Enzyme Genetic Polymorphism rs4343 as Risk of Diabetic Nephropathy in Jambi-Malay Population

Elfiani Elfiani, Anggelia Puspasari, Cut Wulan Arif, C. Maharani, Z. Ali, N. Suhaimi, I. Effendi, S. Suprapti, N. Shafira
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Abstract

Background: Diabetic nephropathy (DN) is one of the frequent complications of type II diabetes mellitus (T2DM) in Jambi province. Controlling blood glucose and blood pressure does not guarantee DN prevention, since genetic factors may also contribute to this disease. Multi-ethnic studies showed that one of the strongest genetic factors associated with DN was single nucleotide polymorphism rs4343 of angiotensin-converting enzyme (ACE) gene. Study regarding phenotype-genotype association of ACE rs4343 and DN has not yet been performed in Jambi Province, which is dominated by Malay ethnicity. This study was conducted to reveal the association between ACE rs4343 and the risk of DN in the Jambi-Malay population.Materials and methods: This was a cross-sectional study involving 75 subjects (44 with DN and 31 without DN) who suffered from T2DM and hypertension. DN was defined as albumin to creatinine ratio (ACR) ≥30 mg/g. Genotyping was performed with one-step tetra amplification refractory mutation system-polymerase chain reaction (PCR) using specific primer for ACE rs4343. Bivariate and multivariate analyses were performed to analyze the genetic risk for DN.Results: The bivariate analysis showed the proportion of DN subjects was higher than non-DN within the AG genotype (11:1) than within the AA (33:30) genotype. This difference was statistically significant (p=0.012; OR (95% CI): 10.00 (1.22-82.15)). Multivariate analysis showed that AG genotype (p=0.047; OR (95% CI): 10.04 (1.03-97.31)) and uncontrolled blood pressure (p=0.001; OR (95% CI): 6.72 (2.08-21.71)) were the risk factors of DN in the Jambi-Malay population.Conclusion: Polymorphism of ACE rs4343 is a risk factor of DN in the Jambi-Malay Population.Keywords: rs4343, angiotensin-converting enzyme gene, diabetic nephropathy, Malay, Jambi
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马来占碑省人群中血管紧张素转换酶基因多态性 rs4343 与糖尿病肾病风险的关系
背景:糖尿病肾病(DN)是占碑省 II 型糖尿病(T2DM)的常见并发症之一。控制血糖和血压并不能保证预防糖尿病肾病,因为遗传因素也可能导致这种疾病。多种族研究表明,与 DN 相关性最强的遗传因素之一是血管紧张素转换酶(ACE)基因的单核苷酸多态性 rs4343。有关血管紧张素转换酶(ACE)基因 rs4343 与 DN 的表型-基因型关联的研究尚未在以马来人为主的占碑省开展。本研究旨在揭示占碑省马来人群中 ACE rs4343 与 DN 风险之间的关联:这是一项横断面研究,涉及 75 名患有 T2DM 和高血压的受试者(44 名 DN 患者和 31 名非 DN 患者)。白蛋白与肌酐比值(ACR)≥30 mg/g定义为DN。使用 ACE rs4343 的特异引物,通过一步法四扩增难治性突变系统聚合酶链反应(PCR)进行基因分型。对 DN 的遗传风险进行了双变量和多变量分析:双变量分析显示,AG 基因型(11:1)的 DN 受试者比例高于 AA 基因型(33:30)的非 DN 受试者比例。这一差异具有统计学意义(P=0.012;OR (95% CI):10.00 (1.22-82.15))。多变量分析表明,AG 基因型(p=0.047;OR(95% CI):10.04(1.03-97.31))和未控制的血压(p=0.001;OR(95% CI):6.72(2.08-21.71))是占碑马来人群中 DN 的风险因素:关键词:rs4343;血管紧张素转换酶基因;糖尿病肾病;马来人;占碑省
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