同型半胱氨酸代谢相关酶基因多态性与先天性心脏病的关系

目的研究同型半胱氨酸相关酶中亚甲基四氢叶酸还原酶(MTHFR)、蛋氨酸合成酶(MS)和蛋氨酸合成酶还原酶(MTRR)基因的多态性与先天性心脏病(CHD)的相关性。方法采用病例对照研究方法,以132例CHD患儿(疾病组)与107名健康儿童(对照组)的血白细胞为样本,应用聚合酶链反应-限制性片段长度多态性技术检测两组的MTHFR基因第677位点、MS基因第2756位点及MTRR第66位点的多态性,比较两组各自的基因型和等位基因的分布频率。结果MTHFR的677位点CC、CT和TT基因型在疾病组中分别为22.73%、51.52%、25.76%,在对照组中分别为42.99%、44.86%、12.15%,两组的分布频率差异有统计学意义。MS基因第2756位点AA、AG和GG基因型在疾病组和对照组中的分布频率差异无统计学意义。MTRR基因第66位点AA、AG和GG基因型在疾病组分别为25.00%、63.64%、11.36%,在对照组中分别为48.60%、42.05%、9.35%,两组的分布频率差异有统计学意义。结论①MTHFR及MTRR的基因多态性与CHD的发病具有一定程度的相关性,MS基因的多态性分布与CHD的发病无关;②MTHFR基因第677位点中的C/C及MTRR第66位点中的A/A均为CHD的保护基因;③两基因变异在CHD的发病中可能有协同作用。

Relationship between genetic polymorphism of homocysteine metabolism enzyme and congenital heart disease

Objective To detect the distribution of polymorphism of MTHFR gene, MS gene and MTRR gene in children with congenital heart disease (disease group )and normal controls. Methods Polymorphism of the 667th site C/T of MTHFR gene, the 2756th site A/G of MS gene and the 66th site A/G of MTRR gene was detected by polymerase chain reaction-restrction fragment length polymorphism in disease group (n=132) and normal controls(n=107). Results To the 667th site of MTHFR gene the frequencies of CC, CT and TT genotypes were 22.73%, 51.52%, and 25.76% in disease group, while 42.99%, 44.86% and 12.15% in normal controls. A significant difference was seen in the distribution frequency in two groups. No significant difference was seen in the distribution frequency of the 2756th site of MS gene in disease group and normal controls. To the 66th site of MTRR gene the frequencies of AA, AG and GG genotypes were 25.00%, 63.64%and 11.36% in disease group,while 48.60%, 42.05% and 9.35% in normal controls. A significant difference was seen in the distribution frequency in two groups. Conclusion The distribution frequency of MTHFR gene and MTRR gene have something to do with morbility of congenital heart disease. While the distribution frequency of MS gene have nothing to do with it. Genotypes C/C in MTHFR gene and A/A in MTRR gene may have a protective effect against congenital heart disease. There may exist some interaction between polymorphisms of MTHFR gene MTRR gene in the pathogenesis of congenital heart disease.