CBS gene variations and serum homocysteine level associated with congenital heart defects

目的 探讨核心家庭胱硫眯β-合酶(CBS)基因变异与子代发生先天性心脏病(CHDs)的关系.方法 选择辽宁省234名CHDs患者(男116人,女lJ8人)及其生物学父母作为病例组;选取同地区无出生缺陷病史及家族史的136名正常人(男78人,女58人)及其生物学父母作为对照组.所有研究对象均采集血样,提取血凝块DNA,分别以PCR和PCR-ARMS方法检测CBS基因844ins68和G919A住点基因型;对部分家庭的母亲和子代以荧光免疫偏振法检测血清tHey水平.结果 各组人群CBS基因844ins68和G919A位点基因型分布已达到Hardy-Weinberg遗传平衡.CBS 844ins68位点分析表明,与纯合野生型(DD)相比,母亲、父亲、子代杂舍子(DI)的比值比[ORs(95%C/)]值分别为14.19(2.21,591.52)、4.37(1.24,23.47)和4.77(1.38,25.37).CBS基因G919A位点分析表明,与GG基因型相比,杂合子GA和纯合子AA的ORs(95%CI)值分别为0.45(0.23,0.87)和0.34(0.11,1.01);母亲GA、父亲GA和AA基因型携带者其子代罹患先心病的危险性均明显降低,ORs(95%CI)值分别为0.44(0.23,0.84)、0.54(0.29,1.00)和0.24(0.08,0.71).基因型联合分析表明,与无危险等位基因的基因型组合(0组)相比,母亲、父亲、子代携带2个危险等位基因者(组2)的ORs(95%CI)值分别为4.32(1.07,20.66)、3.43(0.88,13.71)和8.62(1.69,82.72),且均有统计学意义.不同组别血清tHey水平比较表明.病理组与对照组they水平无明显差异,CBS不同基因型间tHey水平差异亦无显著性(P>0.05).结论 CBS基因844ins68位点杂合子(DI)以及G919A位点突变等住基因(A)与先心痛高危险性有关,但对血清tHcy水平无明显影响.To study the relationship between two common CBS gene variations, tHcy level and CHDs in a nuclear family-based study.234 Chinese CHDs patients and their biological parents were recruited as case groups. And another 136 normal individuals and their parents were recruited as controls. The CBS gene 844ins68 and G919A variants were analyzed by PCR and PCR-ARMS methods. The serum fasting total homocysteine (tHcy) level was detected by Fluorescence Polarization Immunoassay.CBS 844ins68 variant was associated with high risk of CHDs, the odds ratios (ORs) between heterozygotes (DI) versus wild homozygotes (DD) were 14.19 (95% CI: 2.21-591.52), 4.37 (95% CI: 1.24-23.47) and 4.77 (95% CI: 1.38-25.37) in mothers, fathers and offspring respectively (P < 0.05). CBS G919A was significantly associated with low risk of CHDs. The ORs of offspring between heterozygotes (GA) and mutant homozygotes (AA) versus wild homozygotes (GG) were 0.45 (95% CI: 0.23-0.87) and 0.34 (95% CI: 0.11-1.01), P < 0.05. And the parents carrying GA and AA genotypes also was lower risk of CHDs. For both of above two variants, the significant relations occurred especially in ventricular septal defect subgroup. Genotype combination analysis showed the more risk alleles (I and G) the family members carried, the higher the offspring risk of CHDs. And the serum fasting tHcy level was not significantly different among various groups and genotypes.CBS gene 844ins68 and G919A variations in nuclear families could be associated with CHDs risk of offspring, but not with serum fasting tHcy level.国家自然科学基金面上项目; 教育部新世纪人才支持计划PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)04463-4673