Abstract: Background　ADP-ribosylation factor-like protein 15（ARL15） rs4311394 and peroxisome proliferator-activated receptor-γ coactivator 1α（PGC-1α） rs7656250 have been demonstrated to be closely correlated with dyslipidemia，a key risk factor for diabetic kidney disease （DKD），but whether these gene loci have an association with DKD remains unknown. Objective　To explore the association of single nucleotide polymorphisms （SNPs） of ARL15 and PGC-1α genes with DKD. Methods　Participants were China's Han and Korean individuals who were enrolled during 2018—2019，including 393 with T2DM（T2DM group，including 205 Han and 188 Korean cases），and 90 with DKD（DKD group，including 55 Han and 35 Korean cases） from Yanbian University Hospital and Yanji Municipal Hospital，and 268 workers with normal glucose tolerance （NGT） undergoing physical examination in Yanbian University Hospital （NGT group，including 137 Han and 131 Korean cases）. Data were collected，comprising physiological and biochemical indicators，alleles and genotypes of ARL15 rs4311394 and PGC-1α rs7656250 detected by single-base extension assay，and levels of ARL15 and adiponectin proteins detected using ELISA. Results　The results exhibited no statistically significant differences regarding both allele and genotype frequencies of ARL15 rs4311394 and PGC-1α rs7656250 between Han and Korean cases in the NGT group （P>0.05）. Also，the differences in both allele and genotype frequencies of ARL15 rs4311394 and PGC-1α rs7656250 across three groups were not statistically significant （P>0.05）. In addition，no statistically significant differences were noted in allele and genotype frequencies of ARL15 and PGC-1α gene loci among the three groups （P>0.05）. However，the FPG level was higher in carriers of CT genotype of PGC-1α rs7656250 than in carriers of CC or TT genotype of PGC-1α rs7656250 （P<0.05）. The adiponectin protein level was lower in carriers of CT or TT genotype of PGC-1α rs7656250 than in carriers of CC genotype of PGC-1α rs7656250，and also lower in carriers of TT genotype of PGC-1α rs7656250 than in carriers of CT genotype of PGC-1α rs7656250 （P<0.05）. Besides，the adiponectin protein level in T2DM patients was lower than that in individuals with NGT （P<0.05）. And ARL15 and adiponectin protein levels in DKD patients were higher than those in individuals with NGT and T2DM patients （P<0.05）. Furthermore，Spearman's correlation analysis suggested a positive correlation between ARL15 level and adiponectin level （rs=0.372，P<0.05）. Conclusion　Although SNPs in ARL15 and PGC-1α shared no correlation with DKD，the adiponectin protein level was reduced in carriers of CT or TT genotype of PGC-1α rs7656250.

Key words: Diabetic kidney disease；ADP ribosylation factor-15；Peroxisome proliferator receptor &gamma, coactivator 1α；Polymorphism, single nucleotide ；Genotype ；Correlation of data

摘要： 背景　ADP-核糖基化样因子15（ARL15）基因rs4311394位点和过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α）基因rs7656250位点已被证实与血脂紊乱密切相关，而血脂紊乱作为糖尿病肾脏疾病（DKD）的重要危险因素之一，其是否与DKD存在相关性尚未可知。目的　探究ARL15、PGC-1α基因单核苷酸多态性（SNP）与DKD的相关性。方法　选取2018—2019年于延边大学附属医院和延吉市医院确诊的朝鲜族和汉族2型糖尿病（T2DM）患者393例（记为T2DM组）、DKD患者90例（记为DKD组），同期选取在延边大学附属医院进行单位体检的健康人268例〔记为糖耐量正常组（NGT组）〕。检测所有受试者生理、生化指标，采用单碱基延伸法检测ARL15、PGC-1α基因rs4311394、rs7656250位点基因型，酶联免疫吸附试验（ELISA）法检测ARL15、脂联素蛋白水平。结果　NGT组中汉族137例，朝鲜族131例；T2DM组中汉族205例，朝鲜族188例；DKD组中汉族55例，朝鲜族35例。NGT组汉族和朝鲜族人群ARL15基因rs4311394位点、PGC-1α基因rs7656250位点等位基因频率、基因型频率比较，差异无统计学意义（P>0.05）。三组ARL15基因rs4311394位点、PGC-1α基因rs7656250位点等位基因频率、基因型频率比较，差异无统计学意义（P>0.05）。三组ARL15、PGC-1α基因联合位点等位基因频率、基因型频率比较，差异无统计学意义（P>0.05）。携带PGC-1α基因rs7656250位点CT基因型受试者空腹血糖（FPG）水平高于CC、TT基因型受试者（P<0.05）；携带PGC-1α基因rs7656250位点CT、TT基因型受试者脂联素低于CC基因型受试者，TT基因型受试者脂联素低于CT基因型受试者（P<0.05）。T2DM组患者脂联素低于NGT组（P<0.05）；DKD组患者ARL15、脂联素高于NGT组、T2DM组（P<0.05）。Spearman秩相关分析结果显示，ARL15与脂联素呈正相关（rs=0.372，P<0.05）。结论　ARL15、PGC-1α基因SNP与DKD不相关，但携带PGC-1α基因rs7656250位点CT、TT基因型人群的脂联素水平下降。

关键词: 糖尿病肾脏疾病；ADP-核糖基化样因子15；过氧化物酶体增殖物激活受体γ辅激活因子1α；多态性, 单核苷酸；基因型；数据相关性