Parental transmission effects of the PAX7 Polymorphisms among non-syndromic cleft lip palate: A case-parent trio study

Abstract

Background: Orofacial clefts (OFCs) are the most common congenital deformities in the human face, with a prevalence of around 1:800 to 1:1000 among the Indian population. Aim: To assess the Paired box 7 (PAX7) gene polymorphisms in the etiology of non-syndromic cleft lip and cleft palate (NSCL/P) in the Indian population using a case-parent trio design and to contemplate parent-of-origin effects. Materials and Methods: The study comprised forty case-parent trios of NSCL/P from the Indian population. Genomic deoxyribonucleic acid (DNA) was isolated from the cases and their parents. The polymorphisms rs6659735, rs553934, rs624761, rs609959, and rs4075768 of the PAX7 gene were genotyped using Agena Bio MassARRAY analysis. The transmission disequilibrium test (TDT) was performed using the PLINK software and the pairwise linkage disequilibrium analysis by the Haploview software. Results: The genotyping of the polymorphisms rs6659735, rs553934, rs624761, rs609959, and rs4075768 was done. We found a significant association of the rs6659735 (P-value = 0.03, Odds ratio = 4.5) with NSCL/P in the allelic frequencies of the Indian case-parent trios. In addition, the parent-of-origin effects were observed as the allelic TDT analysis showed a significant paternal transmission of the rs6659735 (P-value = 0.04), whereas the rs553934 (P-value = 0.04) showed an excess maternal transmission. Conclusions: The parent-of-origin effects were observed as the two polymorphisms demonstrated a significant parental transmission. The rs6659735 showed a significant paternal transmission, whereas the rs553934 showed an excess maternal transmission, suggesting that the PAX7 gene may influence the risk of NSCL/P in the Indian population.

Keywords

• case-parent trios
• genotyping
• orofacial clefts
• paired box 7
• parent-of-origin