Genome-wide association study on the relationship between SLC7A1 gene and congenital hypertrophic pyloric stenosis

Abstract

Objective To investigate the candidate genes related to the pathogenesis of congenital hypertrophic pyloric stenosis (CHPS) in the whole genome. Methods A two-step method was used to screen the related genes. (1) Trios composed by the core family of CHPS children and their parents, who presented to Guangzhou First People’s Hospital between August 2006 and October 2010, were selected as subjects. All the subjects were of Han ethnicity. SNP 6.0 (Affymetrix) was used for genome-wide microarray to preliminarily screen out the related candidate genes. (2) For the candidate gene-related SNPs screened in the first step, the samples were amplified for PCR and sequencing, and analyzed by transfer disequilibrium test (TDT) to further verify the correlation between genotype and CHPS. Results A total of 894 135 SNPs were scanned out from 23 core family members, yielding an overall successful scan rate of 98.63%. Several genes were found to be associated with the pathogenesis of CHPS. The SLC7A1 gene (13q12.3) was further studied by validating its rs476506 locus in the 40 core family trios through PCR and sequencing. TDT analysis confirmed that rs476506 is associated with CHPS (χ2=11.524, P=0.0007) . Conclusion In Chinese Han population, SLC7A1 gene polymorphism at rs476506 locus is associated with pathogenesis of CHPS, and therefore can be a candidate gene for CHPS. Key words: Congenital hypertrophic pyloric stenosis; SLC7A1 gene; rs476506; Genome-wide association study