Objective: To investigate the distribution of the single nucleotide polymorphism (SNP) sites in TBX1 gene and the distribution of related haplotypes in the patients with conotruncal defects (CTD) and normal people.
Methods: The genotypes of the 3 selected SNPs: G2857C (rs737868), G2963A (rs28649236), and A6571T (rs28939675) in TBX1 gene were analyzed by PCR-RFLP among 130 patients with CTD and 200 normal people. Contingency table was applied to analyze the frequencies of these SNP genotypes and related alleles. PHASE software was used to construct the haplotypes and analyze the haplotype frequencies in these 2 groups.
Results: There were no significant differences in the allele frequency and genotype rates of the SNPs G2587C and A6571T between the CTD patients and normal controls (all P > 0.05). However, the allele frequency and genotype rates of the SNP G2963A were significant different between he CTD patients and normal controls: the G allele frequency in the CTD patients was 53.8%, significantly higher than that in the normal controls (42.5%, chi(2) = 8.14, P < 0.005); and the AA genotype rate of the CTD patients was 21.6%, significantly lower than that of the controls (38.0%), and the GA genotype rate in the CTD patients was 49.2%, significantly higher than that in the controls (39.0%) (both chi(2) = 9.9, P < 0.05). The haplotype frequencies of G2587/G2963/A6571 and G2587/A2963/T6571 of the CTD patients were 49.2% and 14.6% respectively, both significantly higher than those of the normal controls (36.3% and 9.5% respectively), and the haplotype frequencies of G2587/G2963/T6571 and G2587/A2963/A6571 in the CTD patients were 34.6% and 3% respectively, both significantly lower than those in the normal controls (48.3% and 18% respectively) (chi(2) = 22.39, P < 0.005).
Conclusion: The SNP site G2963A located in the coding-region of TBX1 gene is associated with CTD. The persons with G2963 have higher risk of CTD than those with A2963. The haplotypes constructed with these 3 SNP sites may be linked with the susceptibility gene of CTD.