Yahya Mohd Jokha, Ismail Patimah Binti, Nordin Norshariza Binti, Akim Abdah Binti Md, Yusuf Wan Shaariah Binti Md, Adam Noor Lita Binti, Yusoff Maryam Jamielah
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia.
Department of Human Development and Growth, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia.
Int J Chronic Dis. 2019 Jan 1;2019:2053015. doi: 10.1155/2019/2053015. eCollection 2019.
The unique variants or biomarkers of individuals help to understand the pathogenesis as well as the potential risk of individuals or patients to diabetic nephropathy (DN). The aim of this study was to investigate the association of a genetic polymorphism of monocyte chemoattractant protein-1 (CCL2-rs3917887), chemokine receptor 5 (CCR5-rs1799987), engulfment and cell mortality (ELMO1-rs74130), and interleukin-8 (IL8-rs4073) with the development of DN among Malaysian type 2 diabetes mellitus (T2DM) patients. More than one thousand diabetic patients were examined and a total of 652 T2DM patients were tested comprising 227 Malays (nonnephrotic=96 and nephrotic=131), 203 Chinese (nonnephrotic=95 and nephrotic=108), and 222 Indians (nonnephrotic=136 and nephrotic=86). DNA Sequenom mass ARRAY was employed to identify polymorphisms in CCL2, CCR5, ELMO1, and IL8 genes. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models and the best mode of inheritance was chosen. CCR5 rs1799987 (G>A) showed strong association with the development of diabetic nephropathy only among the Chinese with OR=6.71 (2.55-17.68) 95% CI while IL8 rs4073 (T>A) showed association with nephropathy only among the Indians with OR=1.57 (0.66-3.71) 95% CI. The additive model was the best model for the mode of inheritance of all the genes. The contribution of genetic variants differs across ethnic groups or background. Further studies which involve environmental risk factors should be taken into consideration.
个体的独特变异或生物标志物有助于理解个体或患者患糖尿病肾病（DN）的发病机制以及潜在风险。本研究的目的是调查单核细胞趋化蛋白-1（CCL2-rs3917887）、趋化因子受体5（CCR5-rs1799987）、吞噬与细胞死亡（ELMO1-rs74130）以及白细胞介素-8（IL8-rs4073）的基因多态性与马来西亚2型糖尿病（T2DM）患者发生DN之间的关联。对一千多名糖尿病患者进行了检查，共检测了652名T2DM患者，包括227名马来人（非肾病患者=96名，肾病患者=131名）、203名中国人（非肾病患者=95名，肾病患者=108名）和222名印度人（非肾病患者=136名，肾病患者=86名）。采用DNA Sequenom质谱阵列技术鉴定CCL2、CCR5、ELMO1和IL8基因的多态性。从T2DM患者采集的二次血样中提取DNA。使用四种遗传模型对等位基因和基因型进行检测，并选择最佳遗传模式。CCR5 rs1799987（G>A）仅在中国人群中与糖尿病肾病的发生密切相关，OR=6.71（2.55-17.68），95%可信区间；而IL8 rs4073（T>A）仅在印度人群中与肾病相关，OR=1.57（0.66-3.71），95%可信区间。加性模型是所有基因遗传模式的最佳模型。遗传变异的贡献因种族群体或背景而异。应考虑进一步开展涉及环境危险因素的研究。
