母亲与婴儿亚甲基四氢叶酸还原酶C677T多态性与早产和低出生体重的相关性研究(英文)  

Mother’s and child’s methylenetetrahydrofolate reductase C677T polymorphism is associated with preterm delivery and low birth weight

作　　者：陈大方[1] 胡永华[2] 杨帆 吴白燕[1] 陈枥[1] 方治安 王黎华[2] 

机构地区：[1]北京大学基础医学院细胞生物与遗传学系,北京100083 [2]北京大学公共卫生学院流行病学与卫生统计学系 [3]安徽生物医学研究所安庆分所

出　　处：《北京大学学报（医学版）》2004年第3期248-253,共6页Journal of Peking University:Health Sciences

摘　　要：目的 :探讨早产和低出生体重与母亲和婴儿 5 10亚甲基四氢叶酸还原酶基因 (MTHFR)C6 77T多态性的关系。方法 :采用病例对照及核心家系的研究设计 ,共调查了 5 0 0个核心家系 ,包括 2 5 0个正常孕周出生的核心家系和 2 5 0个早产核心家系。采用盐沉淀法提取基因组DNA ,通过聚合酶链式反应 (PCR)对 5 10亚甲基四氢叶酸还原酶基因C6 77T多态性进行基因型鉴定。通过SAS软件的广义线性模型 (GENMOD) ,选用对数线性模型 (Log linearModel)中的泊松回归进行最大拟然比检验 (MaximumLikelihoodRatioTest) ,分析母亲和婴儿MTHFR基因分别与早产和低出生体重的关系。结果 :首先 ,我们采用TDT方法分别检验了早产和低出生体重对照核心家系MTHFR 6 77T等位基因传递是否平衡 ,研究结果表明MTHFR 6 77T突变等位基因传递符合孟德尔遗传规律。之后 ,我们分析了MTHFR基因与早产和低出生体重的关系。结果显示 :婴儿MTHFRCT和TT基因型不但增加早产的发生危险性且具有显著的统计学意义 (CT基因型 :OR =2 .0 1,95 %CI为 1.2 1～ 3.32 ;TT基因型 :OR为 1.82 ,95 %CI为 1.0 2～ 3.26 ) ,而且婴儿MTHFR基因能够增加低出生体重的发生危险且具有显著的统计学意义 (CT基因型 :OR =1.87,95 %CI为 1.0 8～ 3.2 4 ;TT基因型 :OR =1.Objective: To investigate the association of the C677T polymorphism of the 5,10-methyleneterahydrofolate reductase(MTHFR) gene with preterm delivery(PTD) and low birth weight (LBW). Methods: A total of 250 normal gestational age families and 250 PTD families were enrolled in the study. Polymerase Chain Reaction (PCR) followed by restriction enzyme digestion were used for genotyping the polymorphism of MTHFR C677T. A Maximum Likelihood Ratio Test approach based on the log-linear model was used to analyze the relationship of MTHFR gene polymorphism and risk of PTD and LBW. Results: Firstly, we checked the Mendelian transmissions of the variant alleles of MTHFR 677T in PTD and LBW control-parent-triads using TDT test, respectively. These analyses of controls support Mendelian transmission. When children’s genotypes were considered, the MTHFR CT and TT genotypes could significantly increase the risk of PTD and LBW, compared to the genotype of MTHFR CC, the odds ratio and 95% confidence interval (CI) for MTHFR CT and TT genotypes were 2.01,1.21-3.32;1.82, 1.02- 3.26 in PTD group, and were 1.87, 1.08 -3.24; 1.90, 1.02-3.54 in LBW group respectively. When mother’s genotypes were considered, the MTHFR gene polymorphism was not associated with PTD and LBW. Meanwhile, we also examined the association of mothers’ and children’s combined genotypes of MTHFR C677T with the risk of PTD and LBW, and did not find any significant interaction between mothers’ and children’s genotypes. Conclusion: The infant MTHFR CT and TT genotypes are responsible for mothers’ PTD and LBW in our study population. It supports that the non-Mendelian transmission among preterm children is due to a causal association between the MTHFR 677T variant alleles and preterm delivery,and MTHFR gene likely affects LBW via shortened gestation (PTD).

关 键 词：母亲 婴儿 亚甲基四氢叶酸还原酶 C677T多态性 早产 低出生体重 基因型 

分 类 号：R722.6[医药卫生—儿科] R977.3[医药卫生—临床医学]