rs4752028

This replication study investigated common and rare variants in PAX7 and VAX1 genes associated with non-syndromic cleft lip with or without palate (CL(P)). Using TDT analysis in case-parent triads and family-based sequencing of 1,326 individuals from four populations, the study confirmed strong associations with VAX1 markers rs7078160 (p=7.4E-09 in combined samples) and rs4752028 (p=9.8E-06), replicated previous GWAS findings in Asian populations, and identified eight rare missense mutations in PAX7 and two in VAX1 that may contribute to CL(P) etiology.

A systematic review and meta-analysis of 7 case-control studies (3,002 total participants: 1,483 cases and 1,519 controls) examined the association between VAX1 polymorphisms rs7078160 and rs4752028 with non-syndromic cleft lip with or without cleft palate (NSCL/P). For rs7078160, the AA genotype conferred increased NSCL/P risk (OR = 2.34, 95% CI: 1.55-3.24) compared with GG, and AG carriers also showed increased risk (OR = 1.31, 95% CI: 1.11-1.54). For rs4752028, CC carriers showed increased risk (OR = 1.47, 95% CI: 1.09-1.97) and CT carriers (OR = 1.28, 95% CI: 1.01-1.52). Associations were stronger in non-Chinese populations with evidence of publication bias for rs4752028.

A systematic review and meta-analysis of 7 case-control studies (1,483 cases and 1,519 controls) evaluated the association of VAX1 polymorphisms rs7078160 and rs4752028 with non-syndromic cleft lip with or without cleft palate (NSCL/P). For rs7078160, the AA genotype showed significantly increased NSCL/P risk versus GG (OR = 2.34, 95% CI: 1.55-3.24), and AG carriers also showed increased risk (OR = 1.31, 95% CI: 1.11-1.54). For rs4752028, CC versus TT showed OR = 1.47 (95% CI: 1.09-1.97), and CT versus TT showed OR = 1.28 (95% CI: 1.01-1.52). Stronger associations were observed in non-Chinese populations, though publication bias was detected for rs4752028.