维生素D受体基因多态性与妊娠期糖尿病关系的病例对照研究

李金波; 郭孟竹; 李汪俊; 任庆文; 冯永亮; 杨海澜; 张亚玮; 王素萍; 邬惟为

Abstract

李金波,郭孟竹,李汪俊,任庆文,冯永亮,杨海澜,张亚玮,王素萍,邬惟为.维生素D受体基因多态性与妊娠期糖尿病关系的病例对照研究[J].Chinese journal of Epidemiology,2022,43(9):1455-1461

维生素D受体基因多态性与妊娠期糖尿病关系的病例对照研究

Relationship between vitamin D receptor gene polymorphisms and gestational diabetes mellitus: a case-control study

Received:December 10, 2021

DOI：10.3760/cma.j.cn112338-20211210-00965

KeyWord: 维生素D受体单核苷酸多态性妊娠期糖尿病单倍型

English Key Word: Vitamin D receptor Single nucleotide polymorphism Gestational diabetes mellitus Haplotype

FundProject:国家自然科学基金(81703314);山西省高等学校科技创新项目(2019L0439);山西省留学回国人员科技活动择优资助项目(20210042)

Author Name	Affiliation	E-mail
Li Jinbo	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Guo Mengzhu	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Li Wangjun	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Ren Qingwen	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Feng Yongliang	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Yang Hailan	Obstetrics and Gynecology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
Zhang Yawei	National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Wang Suping	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China
Wu Weiwei	Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan 030001, China Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan 030001, China	wuweiwei2008@sina.com

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Abstract:

目的探讨维生素D受体（VDR）基因多态性与妊娠期糖尿病（GDM）之间的关系，为GDM的机制研究提供线索与依据。方法采用病例对照研究设计，以2012年3月1日至2014年7月30日在山西医科大学第一医院产科分娩的孕妇为研究对象，其中334例被诊断为GDM，按年龄、妊娠时间及居住地1∶1匹配相应健康对照。对研究对象进行DNA基因分型，剔除基因分型缺失率>10%者，最终323例病例和320例对照纳入研究。在共显性、显性、隐性和等位基因遗传模型下，通过非条件logistic回归分析VDR基因位点多态性和GDM之间的关系，并采用Haploview软件分析单倍型与GDM之间的关系。结果在基因水平上，VDR基因与GDM发病风险有关（P<0.05）。在调整孕前BMI、糖尿病家族史后，rs7967152位点在共显性（AC vs. AA，OR=1.58，95%CI：1.13~2.21）、显性（AC+CC vs. AA，OR=1.58，95%CI：1.15~2.18）和等位基因（C vs. A，OR=1.41，95%CI：1.10~1.82）遗传模型下与GDM风险升高有关；rs2238140位点在共显性（AA vs. GG，OR=2.24，95%CI：1.19~4.20）、显性（GA+AA vs. GG，OR=1.48，95%CI：1.07~2.03）和等位基因（A vs. G，OR=1.43，95%CI：1.11~1.83）遗传模型下与GDM风险升高有关。在共显性和显性遗传模型下，孕妇携带rs2853564位点AG基因型、AG+GG基因型（OR=1.46，95%CI：1.04~2.05；OR=1.45，95%CI：1.05~2.00）与携带AA基因型相比，是GDM的危险因素；孕妇携带rs2853566位点AG基因型、AG+GG基因型（OR=1.43，95%CI：1.03~2.00；OR=1.41，95%CI：1.02~1.94）与携带AA基因型相比，是GDM的危险因素。在VDR基因内由rs1544410、rs7967152组成的单倍型区块，其GC单倍型与是GDM的危险因素（OR=1.50，95%CI：1.15~1.97）。结论 VDR基因rs7967152、rs2238140、rs2853564、rs2853566位点多态性和区块（rs1544410、rs7967152）GC单倍型与GDM的发病风险升高有关。

English Abstract:

Objective To investigate the relationship between vitamin D receptor (VDR) gene polymorphisms and gestational diabetes mellitus (GDM) and provide evidence for the study of the mechanism of GDM.Methods A case-control study design was used to study pregnant women who delivered in the obstetrics department of the First Hospital of Shanxi Medical University from March 1,2012 to July 30,2014.Of these,334 cases were diagnosed with GDM and were matched 1:1 by age,gestation time and residence to corresponding healthy controls.DNA genotyping was performed for the study subjects,and those with genotyping deletions>10% were excluded.Finally 323 cases and 320 controls were included in the study.Under co-dominant,dominant,recessive,and allele genetic models,unconditional logistic regression analysis on the relationship between VDR gene locus polymorphism and GDM was conducted.And software Haploview was used to analyze the relationship between haplotype and GDM.Results At the genetic level,VDR gene was associated with the risk of developing GDM (P<0.05).After adjusting for pre-pregnancy body mass index,family history of diabetes,it was found that rs7967152 loci was associated with an increased risk of developing GDM (AC vs. AA,OR=1.58,95%CI:1.13-2.21;AC+CC vs. AA,OR=1.58,95%CI:1.15-2.18;C vs. A,OR=1.41,95%CI:1.10-1.82) and rs2238140 loci was associated with an increased risk of developing GDM (AA vs. GG,OR=2.24,95%CI:1.19-4.20;GA+AA vs. GG,OR=1.48,95%CI:1.07-2.03;A vs. G,OR=1.43,95%CI:1.11-1.83).Carrying rs2853564 locus AG genotype and AG+GG genotype (OR=1.46,95%CI:1.04-2.05;OR=1.45,95%CI:1.05-2.00) compared with carrying AA genotype and carrying rs2853566 locus AG genotype and AG+GG genotype (OR=1.43,95%CI:1.03-2.00;OR=1.41,95%CI:1.02-1.94) compared with carrying AA genotype were risk factors for GDM.Haplotype block consisting of rs1544410,rs7967152 in the VDR gene with GC haplotype was a risk factor for GDM (OR=1.50,95%CI:1.15-1.97).Conclusions VDR gene rs7967152,rs2238140,rs2853564,rs2853566 locus polymorphisms and block (rs1544410,rs7967152) GC haplotype were associated with an incrased risk of developing GDM.

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