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.