摘要
目的先天性巨结肠是一种肠神经系统发育异常导致的先天性消化道畸形。RET基因是其主要致病基因,本研究探讨RET启动子区的两个功能性单核苷酸多态?5G/A和?1A/C与先天性巨结肠遗传易感性的关系。方法以聚合酶链反应(PCR)和直接测序(d irect-squenc ing)分析方法,检测了52例先天性巨结肠病人和120例正常对照者RET?5G/A和?1A/C的基因型,比较不同基因型与先天性巨结肠风险的相关性。结果RET?5AA和?1CC基因型频率在先天性巨结肠患者和正常对照中的分布有显著性差异(P值分别为<0.001和0.003),携带RET?5AA和?1CC基因型者罹患先天性巨结肠的风险分别是携带RET?5GG和?1AA基因型者的11.40倍(95%C I,2.89?53.09)和4.65倍(95%C I,0.98?32.30)。此外,单倍型分析发现,同时携带两种风险等位基因的A—C单倍型者的患病风险比携带G—A型者增高了4.38倍(95%C I,2.53?11.90)。结论RET基因功能性单核苷酸多态?5G/A和?1A/C多态可能是中国人先天性巨结肠的遗传易感因素。
Objective： Hirschsprung＇s disease （HSCR） is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. The major HSCR gene is the receptor tyrosine kinase RET, in which the promoter polymorphisms- 5G/A and -1A/C were identified to be functional. This case- control study examined the contribution of these polymorphisms to susceptibility of HSCR. Methods： Genotypes were determined in 52 patients with HSCR and 120 normal controls. The adjusted odds ratios （ORs） and 95% confidence intervals （Cls） were calculated using logistic regression model. Results ： We found a significantly increased risk of HSCR associated with homozygous genotypes of the RET 5AA or RET 1CC compared with the RET - 5GG （OR = 11.40,95% CI,2.89 - 53.09） or RET - 1AA （OR= 4.65, 95% CI, 0.98 - 32. 30） genotypes, respectively. Furthermore, haplotypes analysis indicated that the A-C haplotype increases the risk of HSCR compared with G-A haplotype. Conclusion： These findings suggest that RET functional polymorphisms - 5G/A and - 1A/C may be genetic susceptibility factors for HSCR among Chinese.
出处
《中国优生与遗传杂志》
2006年第12期22-23,89,共3页
Chinese Journal of Birth Health & Heredity
