Dataset Information

Association between IKBKAP polymorphisms and Hirschsprung's disease susceptibility in Chinese children.

ABSTRACT:

Background

Hirschsprung's disease (HSCR) is a rare congenital disease in which enteric nervous system (ENS) in the distal intestine is absent. HSCR is a disease involving genetic factors and environmental factors. Despite a series of genes have been revealed to contribute to HSCR, many HSCR associated genes were yet not identified. Previous studies had identified that a potential susceptibility gene of HSCR was an inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein (IKBKAP). The study aimed to explore the association of genetic variants in IKBKAP and HSCR susceptibility in southern Chinese children.

Methods

Single nucleotide polymorphism (SNPs) were genotyped by the Mass ARRAY iPLEX Gold system (Sequenom, San Diego, CA, USA) on all samples, which included 1,470 HSCR children (cases) and 1,473 healthy children (controls). The associations between SNPs and HSCR or clinical subtypes were assessed by comparing their allele frequencies in corresponding case and control samples. Different genetic models, including additive, recessive, and dominant models, were tested using PLINK 1.9 software.

Results

Further subgroup analysis revealed rs2275630 as a total colonic aganglionosis (TCA)-specific susceptibility locus. The present study is the first to indicate that IKBKAP rs2275630 were associated with HSCR susceptibility, especially in TCA patients.

Conclusions

We conclude that IKBKAP rs2275630 is a susceptibility gene of HSCR.

SUBMITTER: Wang N

PROVIDER: S-EPMC9253937 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMany publications have evaluated the correlation between RET, PHOX2B polymorphisms and Hirschsprung's disease with conflicting results. We performed this meta-analysis to clarify the association of RET, PHOX2B polymorphisms with HSCR.MethodsWe searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. The combined odds ratio (OR) with 95% CI was calculated to estimate the strength of the association. Heterogeneity and publication bias were also assessed.ResultsIn total, 16 studies concerning RET and 4 studies concerning PHOX2B were included in the meta-analysis. The effects of five polymorphisms of RET (rs1800858, rs1800860, rs1800861, rs10900297, rs2435357) and one polymorphism (rs28647582) of PHOX2B were evaluated. We found a significant correlation between RET polymorphisms and HSCR. For rs1800858, the overall ORs (95% CI) of the A versus G, AA versus GG, AA/AG versus GG and AA versus GG/AG were 3.81 (2.28-6.35); 8.36 (3.45-20.25); 3.59 (1.83-7.02); and 6.60 (3.66-11.89). For rs1800861, the comparison of subjects in the G versus T, GG versus TT, GG/TG versus TT and GG versus TT/TG were 2.85(1.81-4.47); 5.38(2.68-10.80); 3.07(2.17-4.34) and 4.14(1.84-9.30) respectively. For rs10900297, the comparison results showed statistically significant. (OR(C versus A) = 5.05,95%CI = 4.16-6.13; OR(CC versus AA) = 9.73, 95%CI = 5.94-15.94; OR(CC/AC versus AA) = 5.31, 95%CI = 3.27-6.82; OR(CC versus AC/AA) = 7.06,95%CI = 5.60-8.91.) But, for rs1800860, the GG/GA versus AA did not reach statistical association (OR = 3.77, 95% CI = 0.94-15.07) and the G versus A, GG versus AA, GG versus GA/AA were 2.23 (1.60-3.11);4.56 (1.14-18.27); 2.38 (1.66-3.43) respectively. For rs2435357, the T versus C, TT versus CC, TT/TC versus CC and TT versus CC/TC were 4.53 (3.27-6.27); 11.44 (5.67-23.10); 4.04 (2.92-5.57), and 9.01(5.25-15.46).The single polymorphism of PHOX2B gene wasn't related to the risk for HSCR.ConclusionsThis meta-analysis shows a significant association between RET polymorphisms and HSCR.