Jayapalan Jaime J, Muniandy Sekaran, Chan Siew P
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Indian J Hum Genet. 2010 May;16(2):78-86. doi: 10.4103/0971-6866.69351.
Wide inter-ethnic allelic variations of the Angiotensin Converting Enzyme (ACE) i nsertion-deletion (I/D) gene polymorphism were thought to be responsible for the conflicting gene-diabetic nephropathy disease association worldwide. We have investigated the genetic susceptibility of the ACE gene to diabetic nephropathy in the multiethnic Malaysian population.
A total of 137 healthy (control) and 256 diabetic subjects were recruited. The diabetic subjects were further subdivided according to their nephropathy status based on urinary albumin-creatinine ratio (ACR) and glomerular filtration rate (GFR). Triple primer polymerase chain reaction (PCR) was used for ACE I/D genotyping. Subsequently, populationwide genetic analysis and gene-disease association studies were performed.
The genotype frequencies in all subgroups were in Hardy-Weinberg equilibrium. Similar allelic and genotypic frequency of ACE I/D gene polymorphism was observed between healthy controls versus pooled type 2 diabetes mellitus (T2DM) subjects, and normoalbuminuria versus microalbuminuria, macroalbuminuria and End Stage Renal Failure (ESRF) (P > 0.05). Neither ethnicity nor gender exerted any influence on the ACE I/D gene polymorphism (P > 0.05), with the exception of the Chinese ethnic group which exhibited a higher frequency of ID genotype (P = 0.042). A multinomial logistic regression model showed that predictive factors including age, systolic blood pressure (SBP), high density lipoprotein (HDL) and glycosylated hemoglobin (HbA1C) were independently associated with diabetic nephropathy, in that order.
The I/D polymorphism of the ACE gene is not significantly associated with both T2DM and/or diabetic nephropathy in this Malaysian population regardless of ethnicity and gender.
血管紧张素转换酶（ACE）插入/缺失（I/D）基因多态性存在广泛的种族间等位基因变异，这被认为是全球范围内基因与糖尿病肾病疾病关联存在冲突的原因。我们研究了马来西亚多民族人群中ACE基因对糖尿病肾病的遗传易感性。
共招募了137名健康（对照）受试者和256名糖尿病受试者。根据尿白蛋白肌酐比值（ACR）和肾小球滤过率（GFR），将糖尿病受试者进一步按肾病状态进行细分。采用三重引物聚合酶链反应（PCR）进行ACE I/D基因分型。随后，进行全人群遗传分析和基因-疾病关联研究。
所有亚组的基因型频率均处于哈迪-温伯格平衡。在健康对照与合并的2型糖尿病（T2DM）受试者之间，以及正常白蛋白尿与微量白蛋白尿、大量白蛋白尿和终末期肾衰竭（ESRF）之间，观察到ACE I/D基因多态性的等位基因和基因型频率相似（P>0.05）。除华裔人群ID基因型频率较高（P = 0.042）外，种族和性别对ACE I/D基因多态性均无影响（P>0.05）。多项逻辑回归模型显示，包括年龄、收缩压（SBP）、高密度脂蛋白（HDL）和糖化血红蛋白（HbA1C）在内的预测因素依次与糖尿病肾病独立相关。
在该马来西亚人群中，无论种族和性别，ACE基因的I/D多态性与T2DM和/或糖尿病肾病均无显著关联。
