Date of Award



Department of Orthodontics

First Advisor

Marie M. Tolarová

First Committee Member

Mirek Tolar


Introduction: Non-syndromic cleft lip with or without cleft palate (NCL±P) is characterized by a multifactorial etiology with both genetic and environmental factors playing a role in its embryonic development. Recent genetic studies have identified susceptibility loci and genetic variations in several genes that were associated with the risk of developing NCL±P. The purpose of this study was to investigate the association of MSX1, BMP4, TGFβ3, and GSK3β gene variants with NCL±P in a casecontrol data set from Karaikal, India. Methods: The case sample consisted of 331 individuals who were diagnosed with CL (bi/unilateral cleft lip), CLP (bi/unilateral cleft lip and palate), or CP (cleft palate). The control sample consisted of 156 individuals from the same location who were not affected with an orofacial cleft and had a negative family history of NCL±P. Genotype proportions and allele frequencies were determined and compared. Results: We tested differences in proportions of genotypes and allele frequencies in four gene variants. No statistically significant differences were found in single nucleotide polymorphisms (SNPs) of MSX1 rs3821949 and BMP4 rs17563. However, when comparing frequencies of TGFβ3 alleles in bilateral NCL±P cases vs controls, there was a close-to-significant difference at p = 0.069165 found. When frequencies of GSK3β alleles in female NCL±P cases vs female controls were compared, the difference was marginally statistically significant at p = 0.058246. Conclusions: Out of four SNPs studied in this Indian population, a possible association with NCL±P was found for GSK-3β rs13314595 and for TGFβ3 rs3917201. It was previously observed that variants of susceptibility genes may occur only in some cleft populations. Therefore, it is important to perform genetic studies in local populations. Knowledge of the presence of certain SNPs is essential if risk calculations or prevention measures are considered.