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Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China.
J Pediatr Surg. 2009 Sep; 44(9):1805-11.JP

Abstract

BACKGROUND

Hirschsprung disease (HSCR, OMIM 142623) is a complex congenital disorder characterized by intestinal obstructions caused by the absence of the intestinal ganglion cells of the nerve plexuses in variable lengths of the digestive tract. The PHOX2B gene is involved in neurogenesis and disruption of Phox2b in mice results in a HSCR-like phenotype. The first association study of the PHOX2B gene with HSCR derived from Chinese population in Hong Kong; here, we address the question of whether PHOX2B acts as a predisposing factor in HSCR pathogenesis in Chinese population in mainland.

METHODS

To investigate the contribution of PHOX2B to the HSCR phenotype, polymerase chain reaction amplification and direct sequencing were used to screen PHOX2B coding regions and intron/exon boundaries for mutations and polymorphisms in 102 patients with HSCR and 96 ethnically matched controls, in Han Chinese populations of Southeastern China.

RESULTS

In this study, we genotyped 4 single nucleotide polymorphisms (SNPs) (including 1 novel SNP) located within the PHOX2B gene. Statistically significant differences were found for c.701 A > G and IVS2 + 100 A > G, and the log-additive model was accepted as the best inheritance model (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.11-2.87) for IVS2 + 100 A > G. We also showed that the haplotype-A G A N composed of 4 SNPs exhibited significant association with the disease (P = .03); this haplotype was more frequently observed in cases than in controls (OR, 2.31; 95% CI, 1.11-4.82).

CONCLUSIONS

Our study provided further evidence that the PHOX2B gene is involved in the susceptibility to HSCR in the Han Chinese population. Our findings are in accordance with the involvement of PHOX2B in the signaling pathways governing the development of enteric neurons.

Authors+Show Affiliations

Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, 310058, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19735829

Citation

Liu, Cui-Ping, et al. "Association Analysis of the PHOX2B Gene With Hirschsprung Disease in the Han Chinese Population of Southeastern China." Journal of Pediatric Surgery, vol. 44, no. 9, 2009, pp. 1805-11.
Liu CP, Li XG, Lou JT, et al. Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China. J Pediatr Surg. 2009;44(9):1805-11.
Liu, C. P., Li, X. G., Lou, J. T., Xue, Y., Luo, C. F., Zhou, X. W., Chen, F., Li, X., Li, M., & Li, J. C. (2009). Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China. Journal of Pediatric Surgery, 44(9), 1805-11. https://doi.org/10.1016/j.jpedsurg.2008.12.009
Liu CP, et al. Association Analysis of the PHOX2B Gene With Hirschsprung Disease in the Han Chinese Population of Southeastern China. J Pediatr Surg. 2009;44(9):1805-11. PubMed PMID: 19735829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association analysis of the PHOX2B gene with Hirschsprung disease in the Han Chinese population of Southeastern China. AU - Liu,Cui-Ping, AU - Li,Xin-Gang, AU - Lou,Jin-Tu, AU - Xue,Yun, AU - Luo,Chun-Fen, AU - Zhou,Xue-Wu, AU - Chen,Fei, AU - Li,Xiang, AU - Li,Meng, AU - Li,Ji-Cheng, PY - 2008/10/15/received PY - 2008/12/05/revised PY - 2008/12/05/accepted PY - 2009/9/9/entrez PY - 2009/9/9/pubmed PY - 2009/12/16/medline SP - 1805 EP - 11 JF - Journal of pediatric surgery JO - J Pediatr Surg VL - 44 IS - 9 N2 - BACKGROUND: Hirschsprung disease (HSCR, OMIM 142623) is a complex congenital disorder characterized by intestinal obstructions caused by the absence of the intestinal ganglion cells of the nerve plexuses in variable lengths of the digestive tract. The PHOX2B gene is involved in neurogenesis and disruption of Phox2b in mice results in a HSCR-like phenotype. The first association study of the PHOX2B gene with HSCR derived from Chinese population in Hong Kong; here, we address the question of whether PHOX2B acts as a predisposing factor in HSCR pathogenesis in Chinese population in mainland. METHODS: To investigate the contribution of PHOX2B to the HSCR phenotype, polymerase chain reaction amplification and direct sequencing were used to screen PHOX2B coding regions and intron/exon boundaries for mutations and polymorphisms in 102 patients with HSCR and 96 ethnically matched controls, in Han Chinese populations of Southeastern China. RESULTS: In this study, we genotyped 4 single nucleotide polymorphisms (SNPs) (including 1 novel SNP) located within the PHOX2B gene. Statistically significant differences were found for c.701 A > G and IVS2 + 100 A > G, and the log-additive model was accepted as the best inheritance model (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.11-2.87) for IVS2 + 100 A > G. We also showed that the haplotype-A G A N composed of 4 SNPs exhibited significant association with the disease (P = .03); this haplotype was more frequently observed in cases than in controls (OR, 2.31; 95% CI, 1.11-4.82). CONCLUSIONS: Our study provided further evidence that the PHOX2B gene is involved in the susceptibility to HSCR in the Han Chinese population. Our findings are in accordance with the involvement of PHOX2B in the signaling pathways governing the development of enteric neurons. SN - 1531-5037 UR - https://www.unboundmedicine.com/medline/citation/19735829/Association_analysis_of_the_PHOX2B_gene_with_Hirschsprung_disease_in_the_Han_Chinese_population_of_Southeastern_China_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3468(08)01091-9 DB - PRIME DP - Unbound Medicine ER -