马来西亚队列研究 2 型糖尿病患者慢性肾脏病的基因-环境交互作用：病例对照研究。
Gene-environment interaction in chronic kidney disease among people with type 2 diabetes from The Malaysian Cohort project: a case-control study.
机构信息
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia.
Epidemiology and Statistics Unit, Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia.
出版信息
Diabet Med. 2020 Nov;37(11):1890-1901. doi: 10.1111/dme.14257. Epub 2020 May 4.
AIM
To examine the possible gene-environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease.
METHODS
A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses.
RESULTS
Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI).
CONCLUSIONS
Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.
目的
探讨 32 个单核苷酸多态性与环境因素之间可能存在的基因-环境相互作用，这些因素可能改变慢性肾脏病的概率。
方法
本病例对照研究纳入了 600 名 2 型糖尿病患者（300 例慢性肾脏病患者，300 例对照），他们参加了马来西亚队列研究。对慢性肾脏病患者进行回顾性亚分析，以评估从招募阶段开始的慢性肾脏病进展情况。我们使用质谱法对 32 个单核苷酸多态性进行了基因分型。从显著的基因-环境相互作用分析中估计慢性肾脏病的概率和新发现的慢性肾脏病进展的预测率。
结果
四个单核苷酸多态性（eNOS rs2070744、PPARGC1A rs8192678、KCNQ1 rs2237895 和 KCNQ1 rs2283228）和五个环境因素（年龄、性别、吸烟、腰围和高密度脂蛋白）与慢性肾脏病显著相关。基因-环境相互作用分析显示，性别（PPARGC1A rs8192678）、吸烟（eNOS rs2070744、PPARGC1A rs8192678 和 KCNQ1 rs2237895）、腰围（eNOS rs2070744、PPARGC1A rs8192678、KCNQ1 rs2237895 和 KCNQ1 rs2283228）和高密度脂蛋白（eNOS rs2070744 和 PPARGC1A rs8192678）与慢性肾脏病的概率显著相关。亚分析表明，新发现的慢性肾脏病进展的发生率为每 1000 人年 133 例（95%CI：115，153），平均随访时间为 4.78（SD 0.73）年。在 KCNQ1 rs2283228 与两个环境因素（性别和 BMI）之间的基因-环境相互作用中，新发现的慢性肾脏病进展的预测率有显著差异。
结论
我们的研究结果表明，eNOS rs2070744、PPARGC1A rs8192678、KCNQ1 rs2237895 和 KCNQ1 rs2283228 与特定环境因素的基因-环境相互作用可能改变慢性肾脏病的概率。
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