Swan E J, Salem R M, Sandholm N, Tarnow L, Rossing P, Lajer M, Groop P H, Maxwell A P, McKnight A J
Centre for Public Health, Queen's University of Belfast, Belfast, UK.
Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Diabet Med. 2015 Aug;32(8):1104-9. doi: 10.1111/dme.12763. Epub 2015 Apr 13.
To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction.
The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 individuals with diabetic kidney disease) vs. control (n = 903 individuals with diabetes and no renal disease) approach. All people included in the analysis were of white European origin and were diagnosed with Type 1 diabetes before the age of 31 years. Replication was conducted in 5093 people with similar phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates.
A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of effect. Three independent signals (seven SNPs) were common to the replication data for both phenotypes with Type 1 diabetes and persistent proteinuria or end-stage renal disease.
Our results suggest that SNPs in nuclear genes that influence mitochondrial function are significantly associated with diabetic kidney disease in a white European population.
评估可能导致线粒体功能障碍的单核苷酸多态性（SNP）与糖尿病肾病的关联。
采用病例对照研究方法（病例组n = 823例糖尿病肾病患者，对照组n = 903例糖尿病且无肾脏疾病患者），对线粒体基因组以及线粒体功能所必需的1039个核基因进行研究。纳入分析的所有个体均为欧洲白人血统，且在31岁之前被诊断为1型糖尿病。在5093例与发现队列具有相似表型的人群中进行重复验证。使用plink遗传分析工具集进行关联分析，并对相关协变量进行校正。
在线粒体基因组中共评估了25个SNP，但均与糖尿病肾病或终末期肾病无显著关联。影响线粒体功能的核基因中共有38个SNP与糖尿病肾病存在名义上的关联，16个SNP与糖尿病肾病继发的终末期肾病相关，荟萃分析证实了相同的效应方向。对于1型糖尿病合并持续性蛋白尿或终末期肾病这两种表型的重复数据，有三个独立信号（七个SNP）是共有的。
我们的结果表明，在欧洲白人人群中，影响线粒体功能的核基因中的SNP与糖尿病肾病显著相关。
