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

OBJECTIVE

To study the relationship between two common CBS gene variations, tHcy level and CHDs in a nuclear family-based study.

METHODS

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.

RESULTS

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.

CONCLUSION

CBS gene 844ins68 and G919A variations in nuclear families could be associated with CHDs risk of offspring, but not with serum fasting tHcy level.