ADP-核糖基化样因子15与过氧化物酶体增殖物激活受体γ辅激活因子1α基因单核苷酸多态性与糖尿病肾脏疾病的相关性研究

doi:10.12114/j.issn.1007-9572.2021.02.015

中国全科医学 ›› 2021, Vol. 24 ›› Issue (27): 3469-3476.DOI: 10.12114/j.issn.1007-9572.2021.02.015

所属专题：内分泌代谢性疾病最新文章合集；泌尿系统疾病最新文章合集

ADP-核糖基化样因子15与过氧化物酶体增殖物激活受体γ辅激活因子1α基因单核苷酸多态性与糖尿病肾脏疾病的相关性研究

凃影叶1，张洪江1，2，康淳1，杜飞1，2，崔佳慧1，邵薇1，2，袁志敏3，王伟杰4*，杨康鹃1*

1.133002吉林省延吉市，延边大学医学院　2.133002吉林省延吉市，延边大学附属医院　3.050081河北省石家庄市，河北武警总队医院　4.133300吉林省珲春市中医医院
*通信作者：王伟杰，主任医师；E-mail：854586857@qq.com　杨康鹃，博士生导师，教授；E-mail：yangkj@ybu.edu.cn
注：凃影叶和张洪江为共同第一作者

出版日期:2021-09-20 发布日期:2021-09-20
基金资助:
基金项目：延边大学大学生创新创业训练资助项目（202010184001）；国家自然科学基金资助项目（81460158）；吉林省卫生与健康技术创新项目（2020J005）

Association of Single Nucleotide Polymorphisms of ARL15 and PGC-1α Genes with Diabetic Kidney Disease　

TU Yingye1，ZHANG Hongjiang1，2，KANG Chun1，DU Fei1，2，CUI Jiahui1，SHAO Wei1，2，YUAN Zhimin3，WANG Weijie4*，YANG Kangjuan1*

1.College of Medicine，Yanbian University，Yanji 133002，China
2.Yanbian University Hospital，Yanji 133002，China
3.Hebei Armed Police Corps Hospital，Shijiazhuang 050081，China
4.Hunchun Traditional Chinese Medicine Hospital，Hunchun 133300，China
*Corresponding authors：WANG Weijie，Chief physician；E-mail：854586857@qq.com
YANG Kangjuan，Doctoral supervisor，Professor；E-mail：yangkj@ybu.edu.cn
TU Yingye and ZHANG Hongjiang are co-first authors

Published:2021-09-20 Online:2021-09-20

分享到

摘要/Abstract

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

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

凃影叶,张洪江,康淳,等. ADP-核糖基化样因子15与过氧化物酶体增殖物激活受体γ辅激活因子1α基因单核苷酸多态性与糖尿病肾脏疾病的相关性研究[J]. 中国全科医学, 2021, 24(27): 3469-3476. DOI: 10.12114/j.issn.1007-9572.2021.02.015.
TU Yingye,ZHANG Hongjiang,KANG Chun, et al. Association of Single Nucleotide Polymorphisms of ARL15 and PGC-1α Genes with Diabetic Kidney Disease　[J]. Chinese General Practice, 2021, 24(27): 3469-3476. DOI: 10.12114/j.issn.1007-9572.2021.02.015.

参考文献

［1］GUO K F，ZHANG L，ZHAO F Y，et al. Prevalence of chronic kidney disease and associated factors in Chinese individuals with type 2 diabetes： cross-sectional study［J］. J Diabetes Complications，2016，30（5）： 803-810. DOI：10.1016/j.jdiacomp.2016.03.020.
［2］RICHARDS J B，WATERWORTH D，O'RAHILLY S，et al. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels［J］. PLoS Genet，2009，5（12）：e1000768. DOI： 10.1371/journal.pgen.1000768.
［3］李瑷彤. ARL15，PGC-1α，TCF7L2基因SNPs联合作用与延边朝鲜族和汉族2型糖尿病合并大血管病变的相关性研究［D］. 延吉：延边大学，2018.
［4］YANG W B，WANG H L，MAO J T，et al. The correlation between CT features and insulin resistance levels in patients with T2DM complicated with primary pulmonary tuberculosis［J］. J Cell Physiol，2020，235（12）： 9370-9377. DOI：10.1002/jcp.29741.
［5］中华医学会糖尿病学分会微血管并发症学组. 糖尿病肾病防治专家共识（2014年版）［J］. 中华糖尿病杂志，2014，6（11）：792-801. DOI：10.3760/cma.j.issn.1674-5809.2014.11.004.
［6］李阳，郭蓉娟，于姚，等. 抑郁症肝郁脾虚证与SIRT1/PGC-1α通路的关联性研究［J］. 广州中医药大学学报，2020，37（12）： 2281-2285. DOI：10.13359/j.cnki.gzxbtcm.2020.12.002.
LI Y，GUO R J，YU Y，et al. Study on correlation of depression of liver depression and spleen deficiency syndrome with SIRT1/PGC-1α pathway［J］. Journal of Guangzhou University of Traditional Chinese Medicine，2020，37（12）： 2281-2285. DOI：10.13359/j.cnki.gzxbtcm.2020.12.002.
［7］李卫平，李启富. PGC-1α与肥胖［J］. 现代医学，2006，34（3）： 204-206.
［8］姚伟列，颜雅青，欧典强，等. 三酰甘油/高密度脂蛋白胆固醇比值与糖尿病并发症的关系研究进展［J］. 中国全科医学，2021，24（17）： 2224-2229. DOI：10.12114/j.issn.1007-9572.2021.00.419.
YAO W L，YAN Y Q，OU D Q，et al. Recent advances in the relationship between plasma triglyceride/high-density lipoprotein cholesterol ratio and diabetic complications［J］. Chinese General Practice，2021，24（17）： 2224-2229. DOI：10.12114/j.issn.1007-9572.2021.00.419.
［9］AMEH O I，OKPECHI I G，AGYEMANG C，et al. Global，regional，and ethnic differences in diabetic nephropathy［J］. Diabet Nephrop，2019. DOI：10.1007/978-3-319-93521-8_3.
［10］REUTENS A T，ATKINS R C. Epidemiology of diabetic nephropathy［J］. Contributions Nephrol，2011，170： 1-7. DOI：10.1159/000324934.
［11］CUI Z W，SHENG T X，WANG Y P，et al. Association between single nucleotide polymorphisms （SNPs） in the gene of ADP-ribosylation factor-like 15 （ARL15） and type 2 diabetes （T2D） in Korean Chinese population in Yanbian，China［J］. Int J Diabetes Dev Countr，2017，37（2）： 124-128. DOI：10.1007/s13410-015-0391-3.
［12］GAYATHRI S B，RADHA V，VIMALESWARAN K S，et al. Association of the PPARGC1A gene polymorphism with diabetic nephropathy in an Asian Indian population （CURES-41）［J］. Metab Syndr Relat Disord，2010，8（2）： 119-126. DOI：10.1089/met.2009.0040.
［13］PARIDA S，SIDDHARTH S，SHARMA D. Adiponectin，obesity，and cancer： clash of the bigwigs in health and disease［J］. Int J Mol Sci，2019，20（10）： E2519. DOI：10.3390/ijms20102519.
［14］LARA-CASTRO C，DOUD E C，TAPIA P C，et al. Adiponectin multimers and metabolic syndrome traits： relative adiponectin resistance in African Americans［J］. Obesity （Silver Spring），2008，16（12）： 2616-2623. DOI：10.1038/oby.2008.411.
［15］DOUMATEY A P，ZHOU J，HUANG H，et al. Circulating adiponectin is associated with renal function independent of age and serum lipids in west africans［J］. Int J Nephrol，2012，2012： 730920. DOI：10.1155/2012/730920.
［16］LIM C C，TEO B W，TAI E S，et al. Elevated serum leptin，adiponectin and leptin to adiponectin ratio is associated with chronic kidney disease in Asian adults［J］. PLoS One，2015，10（3）： e0122009. DOI：10.1371/journal.pone.0122009.
［17］GUO K F，LU J X，HUANG Y，et al. Protective role of PGC-1α in diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling［J］. PLoS One，2015，10（4）： e0125176. DOI：10.1371/journal.pone.0125176.
［18］FONTECHA-BARRIUSO M，MARTIN-SANCHEZ D，MARTINEZ-MORENO J M，et al. The role of PGC-1α and mitochondrial biogenesis in kidney diseases［J］. Biomolecules，2020，10（2）： E347. DOI：10.3390/biom10020347.
［19］IWABU M，YAMAUCHI T，OKADA-IWABU M，et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca（2+） and AMPK/SIRT1［J］. Nature，2010，464（7293）： 1313-1319. DOI：10.1038/nature08991.
［20］NANAYAKKARA P W，LE POOLE C Y，FOUQUE D，et al. Plasma adiponectin concentration has an inverse and a non linear association with estimated glomerular filtration rate in patients with K/DOQI 3 - 5 chronic kidney disease［J］. Clin Nephrol，2009，72（1）： 21-30. DOI：10.5414/cnp72021.
［21］PALMER M B，ABEDINI A，JACKSON C，et al. The role of glomerular epithelial injury in kidney function decline in patients with diabetic kidney disease in the TRIDENT cohort［J］. Kidney Int Rep，2021，6（4）： 1066-1080. DOI：10.1016/j.ekir.2021.01.025.
［22］SANTORO A，GIBERTONI D，MANDREOLI M. p0692non-proteinuric diabetic nephropathy and the risk of mortality in patients with chronic kidney disease （ckd）［J］. Nephrol Dial Transplant，2020，35（Supplement_3）： 692. DOI：10.1093/ndt/gfaa142.p0692.

ADP-核糖基化样因子15与过氧化物酶体增殖物激活受体γ辅激活因子1α基因单核苷酸多态性与糖尿病肾脏疾病的相关性研究

Association of Single Nucleotide Polymorphisms of ARL15 and PGC-1α Genes with Diabetic Kidney Disease

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 0

编辑推荐

Metrics

留言