Negative Association Between lncRNA HOTTIP rs3807598 C>G and Hirschsprung Disease

Background: Hirschsprung disease (HSCR) is a congenital disease that arises from defective intestinal neural system. LncRNA HOTTIP is a critical gene in various diseases, including HSCR. No epidemiological studies have explored the correlation between lncRNA HOTTIP single nucleotide polymorphisms (SNPs) and HSCR risk. We here lead as a pioneer to explore whether SNPs in lncRNA HOTTIP impact the risk of HSCR and HSCR subtypes in an unrelated Chinese population.

Methods: We used the TaqMan method to genotype rs3807598 C>G of the lncRNA HOTTIP gene using 1470 HSCR cases and 1473 healthy controls. Of them, 1441 cases and 1434 controls were successfully genotyped. We adopted odds ratios (ORs) and 95% confidence intervals (CIs) to quantify the relationship.

Results: We got an unexpected outcome that lncRNA HOTTIP SNP rs3807598 C>G could not modify the risk of HSCR (CG vs. CC: adjusted OR=0.89, 95% CI=0.74-1.07; GG vs. CC: adjusted OR=1.10, 95% CI=0.89-1.37; GG/CG vs CC: adjusted OR=0.95, 95% CI=0.80-1.13; and GG vs. CC/CG: adjusted OR=1.19, 95% CI=0.99-1.43). What's more, risk effect of lncRNA HOTTIP rs3807598 C>G is still not obvious in stratification analysis by HSCR subtype.

Conclusion: Our studies did not provide statistical evidence of a correlation between lncRNA HOTTIP SNP rs3807598 C>G and susceptibility of HSCR in the Chinese population that is being studied. Further validation study with a larger sample size covering multi-ethnic groups is warranted.