Association Study Of Five Susceptibility Loci For Nonsyndromic Cleft Lip/Palate In A Chinese Han And Hui Population

Objective Clefts of the lip and palate is among the most common of all humancongenital birth defects,and approximately1in every600newborns worldwide is affected.Clefts of the lip and palate are generally divided into two groups, non-syndromic cleft lip withor without cleft palate(NSCL/P) and syndromic cleft lip with or without cleft palate.Allprevious formal genetic and epidemiological studies have indicated that the etiology ofNSCL/P is multifactorial,with both genetic and environmental factors contributing to thephenotype.Genetic heterogeneity is suggested by differences in the prevalence rates forNSCL/P between populations.Only20%of the genetic susceptibility such as[1q32(IRF6),1p36.3(MTHFR),1q22-1q24(SKI),2p13(TGFA),2q33(SUMO1),4p16(MSX1),6p23-25(F13A,HGP22、 AP2),11q23-q24(PVRL1),14q24(TGFB3),17q21(RARA),19q13(BCL3, TGFB1)]have been identified.Recently, four genome-wide association studies(GWAS) found strong evidence for theassociation between NSCL/P and five chromosomal loci.The study was designed to explore ifgenetic variation in chromosome8q24.21(rs987525),20q12(rs13041247),17q22(rs227731),10q25.3(rs7078160) and1p22.1(rs560426) contributes to nonsyndromic cleft lip with orwithout cleft palate(NSCL/P) in NingXia Hui and Han population.Methods The study group consisted of372NSCL/P(Han=191,Hui=181) patients,theirparents(303fathers,311mothers and158complete families) and498(Han=281,Hui=217)controls.These5SNPs were genotyped by TaqMan SNPs genotyping or PCR-RFLP and thedata was analyzed by case-control analysis, transmission disequilibrium test(TDT),family based association test(FBAT).Results Case-control analysis showed that there were significant differences in thefrequency distributions of both genotypes and alleles in the cleft lip and cleft lip with orwithout cleft palate groups of rs13041247on chromosome20q12(P=0.02,P=0.04,P=0.01,P=0.04),the distribution of alleles at rs227731on chromosome17q22was significantlydifferent between cleft lip and cleft lip with or without cleft palate groups and control in theHans(P<0.05). The distributions of both genotypes and alleles at rs560426in1p22.1genewere also significantly different between cleft lip and cleft lip with or without cleft palategroups and control in the Hans(P<0.05).No significant differences were detected in the Huisat those two loci.Neither allelic nor genotypic association between rs7078160on chromosome10q25and rs987525on chromosome8q24(P=0.07,P=0.20,P=0.58,P=0.33,P=0.35,P=0.59)and NSCL/P was detected in the Hans and the Huis.Conclusions rs13041247single nucleotide polymorphism was associated with NSCL/Pin Ningxia population.rs227731and rs560426single nucleotide polymorphism was associatedwith NSCL/P in Ningxia Han population.rs7078160and rs987525single nucleotidepolymorphism was not associated with NSCL/P in Ningxia population.