Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Manila, Philippines.
Philippine Genome Center, University of the Philippines, Manila, Philippines.
PLoS One. 2024 Nov 19;19(11):e0312291. doi: 10.1371/journal.pone.0312291. eCollection 2024.
Type 2 diabetes mellitus leads to debilitating complications that affect the quality of life of many Filipinos. Genetic variability contributes to 30% to 70% of T2DM risk. Determining genomic variants related to type 2 diabetes mellitus susceptibility can lead to early detection to prevent complications. However, interethnic variability in risk and genetic susceptibility exists. This study aimed to identify variants associated with type 2 diabetes mellitus among Filipinos using a case-control design frequency matched for age and sex. A comparison was made between 66 unrelated Filipino adults with type 2 diabetes mellitus and 121 without. Genotyping was done using a candidate gene approach on genetic variants of type 2 diabetes mellitus and its complications involving allelic association and genotypic association studies with correction for multiple testing. Nine (9) significant variants, mostly involved in glucose and energy metabolism, associated with type 2 diabetes mellitus in Filipinos were found. Notably, a CDKAL1 variant (rs7766070) confers the highest level of risk while rs7119 (HMG20A) and rs708272 (CETP) have high risk allele frequencies in this population at 0.77 and 0.66, respectively, making them potentially good markers for type 2 diabetes mellitus screening. The data generated can be valuable in developing genetic risk prediction models for type 2 diabetes mellitus to diagnose and prevent the condition among Filipinos.
2 型糖尿病会导致使人衰弱的并发症,影响许多菲律宾人的生活质量。遗传变异对 2 型糖尿病风险的贡献率为 30%至 70%。确定与 2 型糖尿病易感性相关的基因组变异可实现早期检测以预防并发症。然而,不同种族之间的风险和遗传易感性存在差异。本研究旨在采用病例对照设计,按年龄和性别进行频率匹配,以鉴定菲律宾人 2 型糖尿病相关的变异。将 66 名无关的菲律宾 2 型糖尿病成年患者与 121 名非 2 型糖尿病患者进行比较。采用候选基因方法对 2 型糖尿病及其并发症的遗传变异进行基因分型,包括等位基因关联和基因型关联研究,并进行了多次测试校正。发现了 9 个与菲律宾人 2 型糖尿病相关的显著变异,这些变异主要涉及葡萄糖和能量代谢。值得注意的是,CDKAL1 变异(rs7766070)赋予了最高水平的风险,而 rs7119(HMG20A)和 rs708272(CETP)在该人群中的高风险等位基因频率分别为 0.77 和 0.66,使其成为 2 型糖尿病筛查的潜在良好标志物。生成的数据对于开发 2 型糖尿病的遗传风险预测模型具有重要价值,可以用于诊断和预防菲律宾人的 2 型糖尿病。