[先天性心脏病与5,10-亚甲基四氢叶酸还原酶基因多态性或叶酸摄入量的相关性研究]

[Study of correlationship between congenital heart disease and 5, 10-methylenetetra hydrofolate reductase gene's polymorphism or folacin intakes].

作者信息

Li Dong, Jing Xue-an, Wang Hua-yi, Ye Wen-jing, Fan Hua

机构信息

Institute of Epidemiology, Taishan Medical University, Tai'an 271016, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2009 Aug;43(8):700-4.

PMID:20021850

Abstract

OBJECTIVE

To investigate the correlationship between congenital heart disease and 5, 10-methylenetetra hydrofolate reductase (MTHFR)'s C677T or folacin intakes, and to study the interaction of them in the occurring of congenital heart disease.

METHODS

We used case-control study (case = 104, control = 208) method. Cases and controls were chosen by age, sex and other conditions. The MTHFR C677T genotype distribution was analyzed by using polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP), and non-conditional and multi-conditional logistic regression analysis were also used to analyze the correlationship and interaction of the factors.

RESULTS

In case group, the number of people in low folacin intake level was 38 (36.54%), which in control group was 21(10.10%). The intake level of folacin during pregnancy was related to congenital heart disease (chi(2) = 31.614, nu = 1, P < 0.0001). The value of OR was 1.417 with 95%CI 1.216 - 1.651, indicating that the low level of folacin intakes was a risk factor to the congenital heart disease. In case group, the number of TT genotype was 46 (44.24%), the number of CT genotype was 42 (40.38%), the number of CC genotype was 16 (15.38%). In control group, the number of TT genotype was 39 (18.75%), the number of CT genotype was 114 (54.81%), the number of CC genotype was 55 (26.44%). A significant genotype distribution difference was identified between case and control group (chi(2) = 23.13, nu = 2, P < 0.0001). Genotype MTHFR 677TT was a risk factor of congenital heart disease and the OR value was 3.437 (95%CI: 2.042 - 5.784). The interaction analysis suggested that the low level of folacin intakes and the MTHFR 677TT genotype had a positive adding effect in the occurring of congenital heart disease. After adjusted some factors such as the ages of parents, fetus age and sex, the effect values of interaction were 13.343 and 15.911 respectively, and the percentages of attributable interaction effects were 0.619 and 0.612. The percentages of effect values of interaction between pure factors were 0.649 and 0.637 and the population attributable risks were 25.26% and 27.82% according to the estimated exposure rate of population risk factors.

CONCLUSION

The low level of folacin intakes during pregancy should be a risk factor to congenital heart disease and the MTHFR 677TT genotype be correlated to congenital heart disease. There is interaction between folacin intakes and the MTHFR 677TT genotype. Increasing the intakes of folacin among MTHFR 677TT genotype people might decrease the incidence rate of congenital heart disease.

摘要

目的

探讨先天性心脏病与5,10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变及叶酸摄入量之间的相关性，并研究它们在先天性心脏病发生中的相互作用。

方法

采用病例对照研究方法（病例组104例，对照组208例）。根据年龄、性别等条件选取病例和对照。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析MTHFR C677T基因型分布，并运用非条件及多条件logistic回归分析各因素的相关性及相互作用。

结果

病例组中叶酸低摄入量水平人数为38例（36.54%），对照组为21例（10.10%）。孕期叶酸摄入量与先天性心脏病有关（χ² = 31.614，ν = 1，P < 0.0001）。OR值为1.417，95%CI为1.216 - 1.651，表明叶酸低摄入量是先天性心脏病的危险因素。病例组中TT基因型46例（44.24%），CT基因型42例（40.38%），CC基因型16例（15.38%）。对照组中TT基因型39例（18.75%），CT基因型114例（54.81%），CC基因型55例（26.44%）。病例组与对照组基因型分布存在显著差异（χ² = 23.13，ν = 2，P < 0.0001）。MTHFR 677TT基因型是先天性心脏病的危险因素，OR值为3.437（95%CI：2.042 - 5.784）。相互作用分析表明，叶酸低摄入量与MTHFR 677TT基因型在先天性心脏病发生中具有正向相加作用。调整父母年龄、胎儿年龄及性别等因素后，相互作用效应值分别为13.343和15.911，归因相互作用效应百分比分别为0.619和0.612。根据人群危险因素暴露率估计，纯因素间相互作用效应值百分比分别为0.649和0.637，人群归因风险分别为25.26%和27.82%。