Genetic association of with long-segment Hirschsprung's disease in southern Chinese children.

BACKGROUND

Hirschsprung's disease (HSCR) is a complex congenital neurodevelopmental disorder affecting colons caused by both genetic and environmental factors. Although several genes have been identified as contributing factors in HSCR, the pathogenesis is still largely unclear, especially for the low prevalent long-segment HSCR (L-HSCR). Gap junction protein alpha 8 () is involved in several physiological processes and has been implicated in several diseases. However, the relationship between single nucleotide polymorphism (SNP) rs17160783 and HSCR in the southern Chinese population remains unknown. The study aimed to explore the association of genetic variants in and HSCR susceptibility in southern Chinese.

METHODS

SNP rs17160783 A>G in was genotyped by TaqMan SNP Genotyping Assay in all samples, which included 1,329 HSCR children (cases) and 1,473 healthy children (controls). Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association of polymorphisms with HSCR susceptibility. The GTEx database and transcription factor binding site (TFBS) prediction were used to analyze the potential regulatory function of rs17160783.

RESULTS

Genetic association analysis illustrated that rs17160783 could increase the risk of L-HSCR (P=0.04, OR =1.48, 95% CI: 1.02-2.14). We also found that expression was increased in HSCR and neurodevelopmentally impaired animal models. External epigenetic data revealed that rs17160783 may have the potential to regulate the expression of the , possibly by altering the binding of transcription factors for , and consequently impacting the PI3K-Akt signaling pathway during the enteric nervous system (ENS) development.

CONCLUSIONS

Our results suggested that rs17160783 might play a regulatory role in expression and increase the susceptibility of L-HSCR in children from southern China.