MSX1 gene polymorphisms in Mexican patients with non-syndromic cleft lip/palate

Abstract Objective Non-syndromic cleft lip/palate malformation (CL/P) is one of the most common birth defects in humans and has a complex etiology involving genetic and environmental factors. Mutations in the MSX1 gene are critical during craniofacial development. The purpose of this study was to investigate the contribution of MSX1 gene polymorphisms to the risk of developing CL/P in a sample of Mexican patients. Methods The sample consisted of 282 subjects (69 cases and 213 relatives). Four single-nucleotide polymorphisms (SNP1, P147Q, SNP5 and P278S) were tested for association with CL/P in triad and case-pseudo-control analyses. Polymorphism typing was performed by restriction fragment length polymorphism and dot-blot techniques. Allele and genotype frequencies were calculated between patients and pseudo-controls and compared using the Chi square test with Yates correction. Odds ratios and 95% confidence intervals were obtained using SPSS software (v19). Triad analysis was also performed using the program HAPLIN (v5.3). Results In the cases and pseudo-controls, an association was found between CL/P and the SNP1-G allele ( P  = 0.031) and the SNP1-G/G genotype ( P  = 0.032), a polymorphism located near MSX1 . Triad analysis showed a tendency toward CL/P susceptibility for the genotype SNP1-G/G ( P  = 0.075) and an association between CL/P and the haplotype GCTC ( P  = 0.037). No associated haplotype was found in the cases and pseudo-controls. Two partial haplotypes, GT (SNP1-SNP5) ( P  = 0.032) and GC (SNP1-P278S) ( P  = 0.033), were associated with susceptibility in the heterozygous and homozygous types, respectively. In contrast, haplotype AT (SNP1-SNP5) was associated with protection ( P  = 0.012) in the homozygous type. Conclusions The results of this study suggest an association between CL/P susceptibility and SNP1, located near the MSX1 gene, in the Mexican population.