Association of selected gene variants with nonsyndromic orofacial clefts in Kuwait.

• This study reports genetic and molecular mechanism of NSOFC in Kuwait. • Significant association of CYRIA rs7552, MSX1 rs3821949, and TGFB3 rs3917201 with NSOFC was demonstrated with a small effect contribution. • The findings of this study support a combined gene effect in craniofacial development and the risk of associated variants in NSOFC. • Our findings have provided insight into the genetic background of NSOFCs in an Arab ethnic group sampled from the Kuwaiti population. Non-syndromic orofacial clefts (NSOFCs) are complex congenital abnormalities involving both environmental and genetic factors involved in orofacial development. This study aimed to investigate the genetic association of specific genetic variants at different CYRIA gene loci with the development of NSOFCs in Kuwait. Four genetic variants (rs7552, rs3758249, rs3821949, and rs3917201) at four selected gene loci (CYRIA , FOXE1 , MSX1 , and TGFB3) were genotyped in a total of 240 DNA samples (patients (n = 114) and random controls (n = 126)) employing TaqMan® allele discrimination assay. For each variant and its genotype, the frequencies were determined and tested for Hardy-Weinberg Equilibrium. Genotype frequencies was compared between patients and controls using Pearson's test. Logistic regression analyses were employed to test for the associations of the four selected variants with the occurrence of NSOFCSs. Significant differences in the distribution of genotypes between cases and controls, rs7552, rs3821949, and rs3917201 were found to have a positive association with NSOFCs. After adjusting for gender, the GG genotype of the rs7552 variant, the AG genotype of the rs3821949 variant, and the CC genotype of the rs3917201 variant showed nearly a two-fold increased risk of NSOFC (p < 0.05). This study reports significant findings on the contribution and modest effect of CYRIA rs7552, MSX1 rs3821949, and TGFB3 rs3917201 in the development of NSOFCs. Our findings provide further evidence on the molecular mechanism and the role of the selected genes in NSOFCs. [ABSTRACT FROM AUTHOR]