Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland.
Folkhälsan Institute of Genetics, Folkhälsan Research Center, 00290 Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, 00290 Helsinki, Finland; Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Curr Opin Genet Dev. 2018 Jun;50:17-24. doi: 10.1016/j.gde.2018.01.002. Epub 2018 Feb 14.
Diabetic kidney disease and other long-term complications are common in diabetes, and comprise the main cause of co-morbidity and premature mortality in individuals with diabetes. While familial clustering and heritability have been reported for all diabetic complications, the genetic background and the molecular mechanisms remain poorly understood. In recent years, genome-wide association studies have identified a few susceptibility loci for the renal complications as well as for diabetic retinopathy, diabetic cardiovascular disease and mortality. As for many complex diseases, the genetic factors increase the risk of complications in concert with the environment, and certain associations seem specific for particular conditions, for example, SP3-CDCA7 associated with end-stage renal disease only in women, or MGMT and variants on chromosome 5q13 associated with cardiovascular mortality only under tight glycaemic control. The characterization of the phenotypes is one of the main challenges for genetic research on diabetic complications, in addition to an urgent need to increase the number of individuals with diabetes with high quality phenotypic data to be included in future genetic studies.
糖尿病肾病和其他长期并发症在糖尿病中很常见,是糖尿病患者合并症和过早死亡的主要原因。虽然所有糖尿病并发症都有家族聚集和遗传性的报道,但遗传背景和分子机制仍知之甚少。近年来,全基因组关联研究已经确定了一些与肾脏并发症以及糖尿病视网膜病变、糖尿病心血管疾病和死亡率相关的易感性位点。对于许多复杂疾病,遗传因素与环境共同增加并发症的风险,并且某些关联似乎特定于特定的情况,例如,SP3-CDCA7 仅在女性中与终末期肾病相关,或 MGMT 和 5q13 染色体上的变异仅在严格控制血糖的情况下与心血管死亡率相关。除了迫切需要增加具有高质量表型数据的糖尿病患者数量以纳入未来的遗传研究之外,对糖尿病并发症的遗传研究的主要挑战之一是对表型进行特征描述。