Abstract: Objective We investigated the relationship between two common CBS gene variations and CHDs in a nuclear family-based study. Methods 234 Chinese CHDs patients and their biological parents were collected as case groups. And another 136 normal individuals and their parents were collected as controls. By PCR and PCR-ARMS methods the CBS gene 844ins68 and G919A variations were analyzed. The serum total homocysteine (tHcy) concentration were detected by Fluorescence Polarization Immunoassay. Results CBS 844ins68 variation 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 associated significantly with low risk of CHDs. The ORs 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) in offspring (P<0.05). And the parents carrying GA and AA genotypes also had lower risk of CHDs. For both of above two loci, 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 risk the offspring had for the happening of CHDs. And the serum fasting tHcy concentration were not significantly different among various groups and genotypes.

Conclusion CBS gene 844ins68 and G919A variations in nuclear families were associated with risk of CHDs in offspring.