Exploring polymorphisms in genes encoding growth factors associated with non-syndromic cleft lip with or without cleft palate and tooth agenesis

Abstract

Objective  To evaluate the association between non-syndromic cleft lip with or without cleft palate (NSCL±P) and tooth agenesis (TA), as well as the association of both conditions with polymorphisms in genes encoding growth factors. Methodology  This cross-sectional study included children with NSCL±P and a control group of children without NSCL±P. Permanent teeth TA (excluding third molars) was evaluated using panoramic radiographs by a trained examiner. Only TA located outside the cleft was considered in the NSCL±P group. Genetic polymorphisms in Transforming Growth Factor Beta 1 (TGFB1)–rs1800470 and rs4803455–Transforming Growth Factor Beta Receptor 2 (TGFBR2)–rs3087465 and rs764522–Epidermal Growth Factor (EGF)–rs4444903 and rs2237051–and Epidermal Growth Factor Receptor (EGFR)–rs2227983– were genotyped by real-time PCR allele discrimination from buccal cell samples. Associations were tested by uni and multivariable Poisson regression models (5% significance level). Results  A total of 243 children–127 with NSCL±P (mean age = 8.80±2.14 years) and 116 without NSCL±P (mean age = 8.58±2.03 years) were included. TA was more frequent in the NSCL±P group (23.8%) than in the control group (6.2%) (p<0.01). The EGF rs2237051 was significantly associated with NSCL±P, independently of the other variables (PRa=1.41; p=0.042). Regarding TA, only the cleft presence was associated with a higher prevalence of TA regardless of different variables (PRa=3.70; p=0.001). There was no association between TA and the investigated genetic polymorphisms. When TA and NSCL±P were considered together, a borderline association was observed with rs1800470 in TGFB1 (p=0.06). Conclusion  NSCL±P is associated with TA outside the cleft area. The EGF rs2237051 was associated with NSCL±P. Polymorphisms in genes encoding growth factors are not associated with TA.