[Association analysis between dystrophin gene polymorphism and non-syndromic cleft lip with or without cleft palate]

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect influenced by genetic and environmental factors, with genetic factors playing a major role. This study aims to investigate the association between the dystrophin (DMD) gene and NSCL/P in a Chinese Han population.

Four tag single nucleotide polymorphisms (SNPs) in the DMD gene were selected and allelic and genotype-based association analyses were performed on 1 780 patients with NSCL/P and 1 823 normal controls.

Comparison with the controls showed that patients with NSCL/P presented three SNPs (rs5971698, rs5928208, and rs5972815) with significant associations with NSCL/P or its subphenotypes. Allelic association analysis revealed that rs5971698 was associated with NSCL/P, unilateral cleft lip with or without cleft palate (UCL/P), left cleft lip with or without cleft palate (LCL/P), unilateral cleft lip and cleft palate (UCLP), left cleft lip and cleft palate (LCLP), unilateral cleft lip (UCL), and left cleft lip only (LCL) (P<0.05); rs5928208 was associated with non-syndromic cleft lip and cleft palate (NSCLP), bilateral cleft lip with or without cleft palate (BCL/P), LCL/P, bilateral cleft lip and cleft palate (BCLP), and LCL (P<0.05); and rs5972815 was associated with UCLP, UCL, and right cleft lip only (RCL)(P<0.05), exhibiting significant laterality bias. Genotype analysis further confirmed these associations. Functional predictions suggested that different alleles at rs5928208 and rs5972815 may influence transcription factor binding affinity.

This study identified associations between SNPs in the DMD gene and NSCL/P in a Western Chinese Han population, providing new evidence for distinct genetic susceptibility loci among NSCL/P subtypes.