Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population

Abstract

Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease.Objectives:The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population.Material and Methods:This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results:The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population.Conclusion:The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.

Association of Single Nucleotide Polymorphisms on Locus 18q21.1 in the Etiology of Nonsyndromic Cleft Lip Palate (NSCLP) in Indian Multiplex Families

“…In a study of the population in southern China, BMP4 rs17563 was reported to be a risk factor for cleft lip only. 17 According to Rafighdoost et al, 18 in the population of southeastern Iran, the BMP4 rs17563 variant has a protective effect on the occurrence of NSCLP. In a separate case-control study by Savitha et al, 19 on NSCLP, one study reported an increased risk of NSCLP in Indian population.…”

Association of single nucleotide polymorphisms in WNT genes with the risk of nonsyndromic cleft lip with or without cleft palate

“…Ethical approval was obtained from ethical committee of Zahedan University of Medical Sciences (IR.ZAUMS.REC.1395.62). The criteria for participants with NSCL/P and healthy individuals were described elsewhere previously (Rafighdoost et al , , ; Rafiqdoost et al ). The controls without the family history of NSCL/P were matched to cases for age, sex, and ethnic background.…”

“…Although, the precise etiology of NSCL/P is unknown, it is proposed that genetic and environmental factors play essential role in the etiology of the disease (Dixon et al 2011). Genetic variants in FGF1 rs34010, CDH1 rs16260, MSX1 rs12532, DHFR 19 bp indel, and BMP4 rs17563 genes are shown to be associated with the risk of NSCL/P in an Iranian population (Rafighdoost et al 2013(Rafighdoost et al , 2015(Rafighdoost et al , 2017Rafiqdoost et al 2014).…”

Analysis of Single Nucleotide Polymorphisms on Locus 13q33.1-34 in Multigenerational Families of Cleft Lip Palate using MassArray

“…(16) According to literature reports, in the population of southeastern Iran, the BMP4 rs17563 variant has a protective effect on the occurrence of NSCLP. (17) In a separate case-control study on NSCLP, one study reported an increased risk of NSCLP in the Indian population. (18) In another candidate gene study, it was reported that in a case-parent trio study on four populations, i.e., Taiwan, Singapore, Korea, and Maryland, RUNX2 rs2819861 polymorphism influenced the risk of NSCLP.…”