Association of ABCA4 gene polymorphisms with nonsyndromic cleft lip with or without cleft palate in a case-parent trio study.

BACKGROUND

Nonsyndromic cleft lip and/or palate (NSCL/P) is a common congenital craniofacial anomaly with multifactorial etiology. Several genome-wide association studies (GWAS) have implicated polymorphisms in ABCA4 gene in correlation to NSCL/P. We conducted a trio-based SNP analysis to evaluate the role of rs560426 and rs4147811 in NSCL/P pathogenesis in an Indian population.

METHODS

Blood samples were collected from 82 trios (father, mother, child), where child is affected by NSCL/P. Genomic DNA was extracted and genotyped for rs560426 and rs4147811 (ABCA4) using PCR Assay. Genotypic distributions were assessed, and transmission disequilibrium test (TDT) was performed on informative trios.

RESULTS

For rs4147811, all individuals across trios were homozygous for the CC genotype, indicating monomorphism in this cohort. For rs560426, 77 trios showed CC genotype while 5 exhibited CG; no GG homozygotes were observed. TDT analysis on heterozygous parents (n=5) revealed borderline transmission bias of the G allele to affected offspring (p<0.05).

CONCLUSION

In this cohort, rs4147811 showed no polymorphism, and rs560426 exhibited variation. These findings suggest that these SNPs may play a role in NSCL/P in this regional population. Larger studies or broader genome-wide approaches may be required to identify relevant genetic risk factors.