Gene-Sex Interaction in Non-Syndromic Orofacial Cleft Subtypes: A Case-Control Study Among the Vietnamese Population.

BACKGROUND

Non-syndromic orofacial clefts (NSOFCs) are one of the common congenital malformations in Vietnam, with 1.4 per 1000 live births, with notable sex differences in occurrence. This case-control study aims to investigate potential sex-specific interactions of WNT3 and NOG polymorphisms across NSOFC subtypes in a Vietnamese population.

METHODS

A total of 720 participants were separated into 4 groups with a male/female ratio of 1:1 (160 individuals with cleft lip and palate (NSCLP), 160 with cleft lip only (NSCLO), 160 with cleft palate only (NSCPO), 240 healthy controls). Two single-nucleotide polymorphisms (SNPs), rs3809857 and rs227731, were genotyped by using the StepOnePlus Real-Time PCR System.

RESULTS

The most significant findings were found in the male NSCLO group under a recessive model of WNT3 rs3809857 after applying Bonferroni correction, as a five-fold protective factor with OR = 0.18 (95% confidence interval: 0.05-0.64, p = 0.0033). Additionally, the weak or moderate protective association between rs3809857 and male NSCLP was found with p < 0.05 under the dominant model. However, there were no significant findings in the female NSOFC subtypes associated with WNT3. Conversely, NOG rs227731 results showed a weak increased risk in female NSCLO and NSCPO with p < 0.05.

CONCLUSION

this study identified the critical role of WNT3 rs3809857 in reducing NSCLO risk in males. These findings support the potential influence of sex as a modifying factor in the genetic susceptibility to non-syndromic orofacial clefts.