rs2166975

A large candidate gene study testing associations between nonsyndromic oral clefts and 12 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) in an Irish population of 509 cleft lip with or without palate (CLP) cases, 383 cleft palate only cases, and 902 controls. The study confirmed associations with PTCH1, SUMO1, and TGFA as contributing to nonsyndromic oral clefts, with PTCH1 P1315L showing significant association with CLP.

This study investigated IRF6 and FGFR1 genes in tooth agenesis (congenital tooth absence) using 116 case/parent trios from Brazil and 89 cases/50 controls from Ohio. The IRF6 V274I variant (rs17015215) was significantly associated with tooth agenesis (P = 0.0006), with an estimated attributable fraction of 16.4%, and preferential association with premolar agenesis. Additional IRF6 markers rs861019 (P = 0.058) and rs7802 (P = 0.004) showed borderline/significant associations. FGFR1 marker rs881301 showed suggestive association with premolar agenesis (P = 0.014). Evidence of gene-gene interactions was found between IRF6 and MSX1 (P = 0.001) and IRF6 and TGFA (P = 0.03).

This family-based transmission disequilibrium test (TDT) study of 112 Lithuanian nuclear families with nonsyndromic orofacial clefts found significant association between TGFA gene marker rs2166975 and cleft palate only (P=0.045), and between D2S292 microsatellite marker and cleft lip with or without palate (P=0.005). The results support TGFA as a genetic modifier of clefting but not as a major causal gene. No associations were found with TGFB3, GABRB3, or RARA loci.