叶酸代谢相关基因多态性与妊娠期糖尿病相关性研究  

Association between folate metabolism-related gene polymorphisms and the risk of gestational diabetes mellitus

作　　者：陈健 李小成[2] 渠慎强 苗苗[4] 郭宝福[2] 王少康[1,5] 孙桂菊 CHEN Jian;LI Xiaocheng;LIANG Shenqiang;MIAO Miao;GUO Baofu;WANG Shaokang;SUN Guiju(Department of Nutrition and Food Hygiene,School of Public Health,Southeast University,Key Laboratory of Environmental Medicine Engineering,Ministry of Education,Nanjing,Jiangsu 210009,China)

机构地区：[1]东南大学公共卫生学院营养与食品卫生学系环境医学工程教育部重点实验室,江苏南京210009 [2]南京市疾病预防控制中心 [3]东南大学医学院附属南京同仁医院 [4]南京市妇幼保健院 [5]西藏民族大学医学院

出　　处：《中国预防医学杂志》2024年第8期1015-1020,共6页Chinese Preventive Medicine

基　　金：中国营养学会科研基金项目(CNS-HPNK2022-140);江苏省研究生实践创新计划项目(SJCX21_0092);南京市医学科技发展项目(YKK19127)。

摘　　要：目的 研究不同遗传模式下,叶酸代谢过程中相关基因多态性与妊娠期糖尿病(gestational diabetes mellitus, GDM)发生风险的相关性,为GDM的个性化预防提供依据。方法2021年9月—2022年9月,南京市妇幼保健院和南京同仁医院同期来院产检的孕妇中按照1∶1配比,将诊断为GDM的孕妇作为研究组,按照孕周相差不超过1周匹配血糖正常的孕妇为对照组,每组各374例。采集糖耐量检测后1周内的空腹外周静脉血,测定两组孕妇血清叶酸、同型半胱氨酸、胰岛素水平;采用SNaPshot SNP分型方法,检测叶酸代谢相关基因多态性(MTHFRC677T、 MTRRA66G、 MTHFRA1298C、 MTRA2756G、RFC1 A80G);使用SNPstats软件分析单个单核苷酸多态性在共显性模型、显性模型、隐性模型、超显性模型、加性模型5种遗传模型下与GDM的相关性。结果 本研究共招募374对孕妇,研究组与对照组孕妇的空腹同型半胱氨酸水平、胰岛素水平、基于稳态模型的胰岛素抵抗指数和胰岛β细胞功能指数差异有统计学意义(t=-7.90、-4.74、-6.29、2.07,P<0.05)。基因测序结果显示,MTHFR C677T位点携带T等位基因的孕妇较未携带者,同型半胱氨酸水平较低(P=0.04),GDM发生风险降低(OR=0.78,95%CI:0.64~0.96), MTRR A66G位点携带G等位基因的孕妇较未携带者,同型半胱氨酸水平较高(P=0.03), GDM的发生风险升高(OR=1.29, 95%CI:1.02~1.63)。结论MTHFRC677T和MTRR A66G位点的基因多态性与GDM的发生风险存在相关性,而MTHFR A1298C、MTR A2756G、RFC1 A80G的基因多态性与GDM的发生风险则无明显相关性,为GDM的精准预防提供了思路与依据。Objective To investigate the correlation between genetic polymorphisms in folic acid metabolism and the risk of gestational diabetes mellitus (GDM) under different genetic patterns to provide evidence for personalized prevention of GDM.Methods From September 2021 to September 2022,374 pregnant women diagnosed with GDM were enrolled as the study group,and 374 pregnant women with normal blood glucose were matched as the control group based on gestational age at the Nanjing Maternal and Child Health Care Hospital and Nanjing Tongren Hospital.According to the ratio of 1∶1,pregnant women with normal blood glucose were selected as the control group of this study.Fasting peripheral venous blood was collected within one week after glucose tolerance test,and serum folic acid (chemiluminescence),homocysteine (circulating enzymatic method),and insulin levels (electrochemiluminescence immunoassay) were measured.The polymorphism of genetic polymorphisms (MTHFR C677T,MTRR A66G,MTHFR A1298C,MTR A2756G,RFC1 A80G) in folic acid metabolism was detected by the SNaPshot SNP typing method.The association between individual single nucleotide polymorphisms and the risk of GDM under five different genetic patterns (codominant,dominant,recessive,overdominant,and additive) was analyzed using the SNPstats software online.Results A total of 374pairs of pregnant women were recruited.There were differences in fasting homocysteine levels,insulin levels,insulin resistance index based on the homeostasis model,and pancreatic β-cell function index between the two groups of pregnant women (t=-7.90,-4.74,-6.29,2.07,P<0.05).The results of gene sequencing showed that pregnant women who carry the T allele at MTHFR C677T had a higher homocysteine level (P=0.04)and a lower risk of GDM compared with non-carriers (OR=0.78,95%CI:0.64-0.96),and pregnant women who carry the G allele at the A66G locus of MTRR have a higher homocysteine level (P=0.03) and a significantly higher risk of developing GDM than non-carriers (OR=1.29,95%CI:1.02-1.63).No significant

关 键 词：妊娠期糖尿病 基因多态性 叶酸代谢 同型半胱氨酸 

分 类 号：R714[医药卫生—妇产科学]