ABSTRACT
The purpose of this study was to investigate the contribution of MSX1 gene to the risk of nonsyndromic cleft lip with or without cleft palate (NS-CL +/- P) in the Korean population. The samples consisted of 142 NS-CL +/- P families (9 with cleft lip, 26 with cleft lip and alveolus, and 107 with cleft lip and palate; 76 trios and 66 dyads). Three single nucleotide polymorphisms (SNPs: rs3821949, rs12532, and rs4464513) were tested for association with NS-CL +/- P case-parent trios using transmission disequilibrium test (TDT) and conditional logistic regression models (CLRMs). Minor allele frequency, heterozygosity, chi2 test for Hardy-Weinberg equilibrium, and pairwise linkage disequilibrium (LD) at each SNP were computed. The family- and haplotype-based association test programs were used to perform allelic and genotypic TDTs for individual SNPs and to fabricate sliding windows of haplotypes. Genotypic odds ratios (GORs) were obtained from CLRMs using R software. Although the family-based TDT indicated a meaningful association for rs3821949 (P = 0.028), the haplotype analysis did not reveal any significant association with rs3821949, rs12532, or rs4464513. The A allele at rs3821949 had a significant increased risk of NS-CL +/- P (GOR, 1.64; 95% confidence interval,1.03-2.63; P = 0.038, additive model). A positive association is suggested between MSX1 rs3821949 and NS-CL +/- P in the Korean population.
Subject(s)
Female , Humans , Male , Alleles , Asian People/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Gene Frequency , Genotype , Haplotypes , Linkage Disequilibrium , Logistic Models , MSX1 Transcription Factor/genetics , Odds Ratio , Polymorphism, Single Nucleotide , Republic of Korea , Risk Factors , SoftwareABSTRACT
Objective:To study TGF? and TGF?3 polymorphisms in patients with nonsyndromic cleft lip with or without cleft palate(NSCLP,CLP or CL)and cleft palate only(CPO).Methods:TGF? and TGF?3 DNA was extracted and amplified from peripheral leukocytes of 56 cases of NSCLP(40 of CLP and 16 of CL),26 of CPO and 28 of unrelated controls.The primers were designed according to the 3'untranslated region of TGF? and 5th exon of TGF?3 published in the Internet.The PCR products were analyzed by single-stranded conformation polymorphism(SSCP).The aim fragments were further conformed by DNA sequencing after being cloned into pGEM-T vector.Results:The 345 bp fragment of TGF? and 193 bp of TGF?3 were amplified from NSCLP,CPO and control samples.In SSCP analysis,three alleles of TGF? and two of TGF?3 were found.Sequencing results showed three DNA polymorphic sites in TGF? and one in TGF?3 which were all base shifts.There was no difference of each genome between patients and controls.Conclusion:There are no direct association between 3'UTR of TGF? or 5th exon of TGF?3 and NSCLP or CPO in Chinese.