Background

Type 2 Diabetes mellitus (T2DM) is a chronic metabolic disorder. It is a major non-communicable disease affecting 463 million people globally in 2019 and is expected to be double to about 700 million by 2045. The majority are Asians with Indian ethnicity in Malaysia reported as the highest prevalence of T2DM. Cardiovascular disease, renal failure, blindness and neuropathy, as well as premature death are the known morbidity and mortality resulted from T2DM. T2DM is characterized by the dysfunctional insulin physiology that causes reduction of glucose transport into the cells which lead to hyperglycaemia. Hence, one of the important treatments is an oral antidiabetic drug that lowers the serum glucose level in patients with T2DM. This drug will be transported across cell membranes by organic cation transporters (OCT). Therefore, it is important to identify the OCT candidate gene polymorphisms related to T2DM especially among the Indian ethnicity in Malaysia.

Methods

Blood samples were collected from 132 T2DM patients and 133 controls. Genotyping of OCT1 (rs628031), OCT2 (rs145450955), OCT3 (rs3088442 and rs2292334) was performed using (PCR-RFLP).

Results

No association was observed for genotypic and allelic distributions in all the gene polymorphisms of OCT genes (P > 0.05). However, a logistic regression analysis stratified by gender in a dominant model showed a significant difference for OCT3 among males with T2DM (P = 0.006). Significant association was also observed for OCT3 when stratified to subjects aged > 45 years old (P = 0.009).

Conclusion

Based on these findings, the association of OCT3 (rs2292334) could be considered as a possible genetic risk factor for the development of T2DM among Indian males alone.

中文翻译：

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马来西亚印裔2型糖尿病患者OCT1、OCT2、OCT3基因多态性分析

背景

2 型糖尿病 (T2DM) 是一种慢性代谢疾病。它是一种主要的非传染性疾病，在 2019 年影响全球 4.63 亿人，预计到 2045 年将增加一倍，达到约 7 亿人。据报道，马来西亚的印度裔亚洲人占 T2DM 的最高流行率。心血管疾病、肾功能衰竭、失明和神经病变以及过早死亡是已知的 T2DM 导致的发病率和死亡率。T2DM 的特征在于功能失调的胰岛素生理学，导致进入细胞的葡萄糖转运减少，从而导致高血糖症。因此，一种重要的治疗方法是口服降糖药，以降低 T2DM 患者的血糖水平。这种药物将通过有机阳离子转运蛋白 (OCT) 转运穿过细胞膜。所以，

方法

从 132 名 T2DM 患者和 133 名对照中采集血样。使用 (PCR-RFLP) 进行 OCT1 (rs628031)、OCT2 (rs145450955)、OCT3 (rs3088442 和 rs2292334) 的基因分型。

结果

OCT基因的所有基因多态性中的基因型和等位基因分布均未观察到相关性（P  > 0.05）。然而，在占主导地位的模型中按性别分层的逻辑回归分析显示 OCT3 在 T2DM 男性中存在显着差异（P  = 0.006）。当分层到年龄 > 45 岁的受试者时，OCT3 也观察到显着相关性（P =  0.009）。

结论

基于这些发现，OCT3 (rs2292334) 的关联可被认为是仅印度男性发生 T2DM 的可能遗传风险因素。