Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Sci Rep. 2021 Feb 2;11(1):2794. doi: 10.1038/s41598-021-82276-3.
Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic associations of comorbid diseases within the framework of the Utrecht Cardiovascular Pharmacogenetic studies by turning information of > 25 years follow-up data of 1237 subjects whom were genotyped and included in the discovery study. We performed Cox proportional-hazards regression to examine associations between genetic variants and comorbid diseases including cardiovascular diseases (CVD), chronic eye disease, cancer, neurologic diseases and chronic kidney disease. Secondly, we replicated our findings in two independent cohorts consisting of 1041 subjects. Finally, we performed a meta-analysis by combining the discovery and two replication cohorts. We ascertained 390 (39.7%) incident cases of CVD, 182 (16.2%) of chronic eye disease, 155 (13.8%) of cancer, 31 (2.7%) of neurologic disease and 13 (1.1%) of chronic kidney disease during a median follow-up of 10.2 years. In the discovery study, we identified a total of 39 Single Nucleotide Polymorphisms (SNPs) associated with comorbid diseases. The replication study, confirmed that rs1870849 and rs8051326 may play a role in the incidence of chronic eye disease in T2D patients. Half of patients developed at least one comorbid disease, with CVD occurring most often and earliest followed by chronic eye disease. Further research is needed to confirm the associations of two associated SNPs with chronic eye disease in T2D.
潜在的遗传决定因素导致 2 型糖尿病（T2D）等未来疾病的发生。本研究旨在确定哪些遗传变异与 T2D 的主要合并症的发病有关。首先，我们通过在乌得勒支心血管药物遗传学研究框架内开展一项关于合并症的遗传关联的发现研究，利用对 1237 名接受基因分型且纳入发现研究的受试者超过 25 年随访数据的信息，来实现我们的目标。我们使用 Cox 比例风险回归来检查遗传变异与包括心血管疾病（CVD）、慢性眼病、癌症、神经疾病和慢性肾病在内的合并症之间的关联。其次，我们在由 1041 名受试者组成的两个独立队列中对我们的发现进行了复制。最后，我们通过合并发现队列和两个复制队列进行了荟萃分析。在中位随访 10.2 年期间，我们确定了 390 例（39.7%）CVD 事件、182 例（16.2%）慢性眼病、155 例（13.8%）癌症、31 例（2.7%）神经疾病和 13 例（1.1%）慢性肾病。在发现研究中，我们总共鉴定出与合并症相关的 39 个单核苷酸多态性（SNP）。复制研究证实，rs1870849 和 rs8051326 可能在 T2D 患者的慢性眼病发病中起作用。一半的患者至少发生了一种合并症，CVD 发生的最常见且最早，其次是慢性眼病。需要进一步的研究来证实这两个与慢性眼病相关的 SNP 与 T2D 慢性眼病之间的关联。
