Parental transmission effect of PDGF-C gene variants on non-syndromic cleft lip with or without cleft palate

Abstract

Platelet derived growth factor -c (PDGF-C) plays a major role in embryogenesis especially during the neural crest cell induction. Animal studies revealed that PDGF signalling is required for orofacial development. Further, Pdgfc knockout mice also showed cleft face phenotype. The present study aims to evaluate the parental transmission effect of PDGF-C gene variants in the etiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) in South Indian population. In the present study 148 triads (case-parents) were genotyped for five single nucleotide polymorphisms (SNPs) in PDGF-C gene (rs983473, rs10517653, rs17035464, rs28999109, rs1002091) using TaqMan allelic discrimination method. Haploview program 4.2 was used to test the alleleic associations by transmission disequilibrium test (TDT) and linkage disequilibrium (LD) between the SNPs. Haplotype transmission effects were analysed using FAMHAP package. Further, the possible parent-of-origin effects were assessed by likelihood based approaches. TDT analysis revealed significant excess transmission of “C” allele from rs983473 and “C” allele from rs1002091 SNPs to the affected child. The sliding window haplotype analysis method showed significant overtransmission of some haplotypes. The analysis of parent of origin effects showed an excess of maternal transmission for C allele of rs983473 SNP (5.48%) and paternal transmission for C allele of rs1002091 SNP (4.12%). The present study supported the parenteral transmission effects of PDGF-C genetic variations the pathogenesis of NSCL/P. As the number of triads included in the study are limited, further studies are needed to confirm this association in other populations with more triads and other markers of PDGF-C.