新疆维、汉族单纯性先天性心脏病MTHFR基因C677T多态性研究

The association study on MTHFR gene polymorphism C677T and simple congenital heart disease in Uyghur and Han populations in Xinjiang

目的分析亚甲基四氢叶酸还原酶基因C677T(rs1801133)多态性及血浆同型半胱氨酸水平与新疆维、汉族单纯性先天性心脏病发病的关系。方法采用循环酶法测定228例(105例汉族和123例维吾尔族)单纯性先天性心脏病患者(CHD组)和230例正常体检者(105例汉族和125例维吾尔族)(对照组)血浆同型半胱氨酸浓度,聚合酶链-限制性片段长度多态性(PCR-RFLP)法对rs1801133基因分型,Sanger核酸测序法验证分型结果;并进行统计学分析。结果新疆维、汉族健康人群血浆同型半胱氨酸水平及基因型频率和等位基因频率分布差异有统计学意义(P<0.05);维、汉族CHD组血浆同型半胱氨酸水平明显高于对照组,差异有统计学意义(P<0.05);CHD组与对照组基因型频率和等位基因频率分布差异均有统计学意义(P<0.05);新疆维、汉族动脉导管未闭、法洛氏四联症患者等位基因频率分布与对照组比较差异有统计学意义(P<0.05)。结论 rs1801133多态性可能是新疆地区维、汉族单纯性先天性心脏病的遗传易感因素并且存在民族异质性,其可能通过影响血清同型半胱氨酸水平参与单纯性先天性心脏病的发病及临床表现。

Objective To examine plasma homocysteine （Hcy） and methylenetetrahydrofolate reductase gene polymorphism C677T（rs1801133） in simple congenital heart disease in Uyghur and Han populations in Xinjiang. Methods 228 （105 Han and 123 Uyghur） CHD patients and 230 （105 Han and 125 Uyghur） normal objects were measured the concentration of plasma Hcy by Enzymatic cycling assay, PCR RFLP was performed to detect the genotype and allele frequencies at rs1801133 site in the Uyghur and Han populations in Xinjiang. Results The difference of plasma homocysteine, genotype frequency and allele frequency distribution between Han and Uyghur healthy populations was statistically significant （P 〈0.05）; Plasma homocysteine level in Uyghur and Han simple congenital heart disease group was significantly higher than those in the control group; The case group and control group genotype frequency and allelefrequency distribution differences were statistically significant （P 〈0.05）. Compared with control group, allele frequency distribution in patent ductus arteriosus and Tetralogy of fallot patients in Uyghur and Han populations were significantly different （P 〈0.05）. Conclusion rs1801133 polymorphism may be genetic susceptibility factors in simple congenital heart disease and existing ethnic heterogeneity, which may influence the plasma homocysteine levels to participate in the pathogenesis of simple congenital heart disease and clinical manifestation.