Dataset Information

A study on genetic polymorphism of RET proto-oncogene in Hirschsprung's disease in children.

ABSTRACT:

Background

Hirschsprung's disease (HD) is a genetic disorder with a complex pattern of inheritance. Some single-nucleotide polymorphisms (SNPs) are identified to be associated with the risk of Hirschsprung's Disease (HSCR).

Aims and objectives

The aim of this study is to know the association between the rearranged during transfection (RET) proto-oncogene polymorphism and HD and to characterize the SNPs of RET proto-oncogene affecting HD.

Materials and methods

The study was conducted in the Department of Pathology in association with the Department of Pediatric Surgery. Blood samples were collected from the patients diagnosed with confirmed HD and from age- and sex-matched controls. This case-control study consisted of 53 HSCR cases and 50 controls. Genotypes of rs1800860 and rs1800861 were analysed in by polymerase chain reaction amplification and sanger sequencing. Associations with the risk of HSCR were estimated by odds ratio (OR) and their 95% confidence intervals (95% CI) using.

Results

We observed that in the case of rs1800860A > G genotype AG was not associated with the increasing risk of disease (OR with 95% CI = 0.568 [0.238-1.356]) while genotype GG was associated with increasing the risk of the disease (OR with 95% CI = 2.278 [0.967-5.366]). In the case of rs1800861G > T genotype GT was associated with lowering the risk of the disease (OR with 95% CI = 0.230 [0.0981-0.539]) while genotype TT was associated with increasing the risk of the disease (OR with 95% CI = 9.647 [3.830-24.302]). The difference in the genotypic distribution of GT and TT at rs1800861G > T between Short segment disease (SSD) cases and Long Segment Disease (LSD) and total colonic aganglionosis was made by Fisher's exact test and it was statistically significant (P = 0.0476 and 0.0054).

Conclusion

The results of this study support the hypothesis that variations in RET pathway might play an important role in the development of HSCR.

SUBMITTER: Kumari M

PROVIDER: S-EPMC8051638 | 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.