[Study of serum Hcy and polymorphisms of Hcy metabolic enzymes in 192 families affected by congenital heart disease].

ABSTRACT

OBJECTIVE: To explore genotype distributions at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci in healthy Chinese living in northern area, and to assess the association of single or combined gene mutations with folic acid, Vit.B(12), Hcy levels and CHD. METHODS: 192 patients having CHD and their biological parents in Liaoning province registered as birth defects were included in this study as case group, and 124 healthy subjects (age and gender matched) and their biological parents were simultaneously selected from the same geographic area as control. To all subjects, the gene polymorphism at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci was examined with PCR-RFLP. The serum folic acid and homocysteine (Hcy) level were analyzed with Radioimmunoassay or fluorescence polarization immunoassay (FPIA). RESULTS: In healthy Chinese living in northern China, the mutant allele frequencies of these four loci were MTHFR 51.18%, MS 7.58%, MTHFD 24.32%, and CBS insertion 2.36%, respectively. The heterozygosity of CBS 844 ins68bp was more prevalent in case than in control (12.57% vs 2.97% in children, 10.88% vs 3.09% in father and 11.54% vs 1.02% in mother, respectively), and yielded an odds ratio (OR) of 4.70 (95% CI 1.34-25.15) in children, 3.83 (95% CI 1.05-20.98) in fathers and 12.65 (95% CI 1.92-532.47) in mothers. There is no existed significant difference at the other three loci. The percents of mothers with MTHFR, CBS and MTHFD gene polymorphisms, of mothers with MTHFR and CBS being polymorphisms (OR=8.44, 95aCI 1.23-362.26), of mothers with MTHFD and CBS being polymorphisms in case were higher than those in control. Serum folic acid levels of mothers and fathers in case were significantly higher than those of counterparts in control. Serum Hcy level of mothers in case was higher than that of counterparts in control without significant difference. Homozygous mutation at MTHFR and MTHFD loci made serum folic acid and Vit.B(12) levels slightly decreased and serum Hcy level increased. CONCLUSION: The study showed presence of ethnic and district difference of gene polymorphisms at these four loci. 68 bp insertion at exon 8 of CBS gene base 844 could be a risk factor for CHD, and the insertion in parents (especially in mothers) could increase CHD risk in offspring.