Alidoust Leila, Sharafshah Alireza, Keshavarz Parvaneh
Department of Medical Genetics, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Ophthalmic Genet. 2024 Jun;45(3):226-232. doi: 10.1080/13816810.2024.2318611. Epub 2024 Mar 21.
Diabetic retinopathy (DR) is recognized as one of the most prevalent complications of diabetes and a major cause of morbidity. Transcription factor 7-like 2 (TCF7L2), a pivotal component in the Wnt-signaling pathway, plays a significant role in β-cell development, blood-glucose homeostasis, cell survival, cell migration, and cell proliferation. Thus, this study aimed to assess the association between TCF7L2 variants (rs7903146, rs11196205, and rs12255372) with DR in a population-based association study.
DNA was extracted from whole blood of all subjects by salting-out procedure. Total 524 T2DM patients including 234 T2DM individuals without DR and 290 T2DM individuals with DR were genotyped by TaqMan assay technology. Clinical characteristics of subjects were conducted to evaluate the plausible association between TCF7L2 variants and DR with univariate linear regression analysis.
Demographic analysis between case and control groups revealed significant differences in FBS, HbA1c, lipidemia, heart disease, and family history of T2DM ( < 0.05). No significant difference was observed in either genotypes distribution or allele frequency ( > 0.05) between T2DM individuals with and without DR in any models of inheritance. Genotype-phenotype association showed no significant association. Result of analysis indicated that HbAlc with adjusted OR of 1.8 ( < 0.0001) and first-degree relatives of family history with adjusted OR of 3.04 ( < 0.0001) were significantly associated with DR. Finally, haplotype analysis showed no noticeable association.
In conclusion, there was no significant genetic association between rs7903146, rs11196205, and rs12255372 with DR among T2DM Iranians; however, these variants may play unknown roles in other populations.
糖尿病视网膜病变（DR）被认为是糖尿病最常见的并发症之一，也是发病的主要原因。转录因子7样2（TCF7L2）是Wnt信号通路中的关键成分，在β细胞发育、血糖稳态、细胞存活、细胞迁移和细胞增殖中发挥重要作用。因此，本研究旨在通过一项基于人群的关联研究评估TCF7L2变异体（rs7903146、rs11196205和rs12255372）与DR之间的关联。
采用盐析法从所有受试者的全血中提取DNA。通过TaqMan检测技术对总共524例2型糖尿病患者进行基因分型，其中包括234例无DR的2型糖尿病个体和290例有DR的2型糖尿病个体。对受试者的临床特征进行单因素线性回归分析，以评估TCF7L2变异体与DR之间可能存在的关联。
病例组和对照组的人口统计学分析显示，空腹血糖（FBS）、糖化血红蛋白（HbA1c）、血脂异常、心脏病和2型糖尿病家族史存在显著差异（<0.05）。在任何遗传模型中，有DR和无DR的2型糖尿病个体之间的基因型分布或等位基因频率均无显著差异（>0.05）。基因型-表型关联显示无显著关联。分析结果表明，校正比值比（OR）为1.8的HbAlc（<0.0001）和校正OR为3.04的家族史一级亲属（<0.0001）与DR显著相关。最后，单倍型分析显示无明显关联。
总之，在伊朗2型糖尿病患者中，rs7903146、rs11196205和rs12255372与DR之间不存在显著的遗传关联；然而，这些变异体可能在其他人群中发挥未知作用。
