Pgt 3rd Year, Department of Pathology, IPGME&R, Kolkata, West Bengal, India.
Assistant Professor, Department of Pathology, IPGME&R, Kolkata, West Bengal, India.
Afr J Paediatr Surg. 2020 Jul-Dec;17(3 & 4):104-107. doi: 10.4103/ajps.AJPS_69_17.
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).
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.
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.
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).
The results of this study support the hypothesis that variations in RET pathway might play an important role in the development of HSCR.
先天性巨结肠（HD）是一种具有复杂遗传模式的遗传疾病。一些单核苷酸多态性（SNP）被确定与先天性巨结肠（HSCR）的风险相关。
本研究旨在了解 RET 原癌基因多态性与 HD 的关系，并确定影响 HD 的 RET 原癌基因的 SNP。
该研究在病理科与小儿外科合作进行。从确诊为 HD 的患者和年龄、性别匹配的对照组中采集血样。这项病例对照研究包括 53 例 HSCR 病例和 50 例对照。通过聚合酶链反应扩增和 Sanger 测序分析 rs1800860 和 rs1800861 的基因型。使用比值比（OR）及其 95%置信区间（95%CI）估计与 HSCR 风险的关联。
我们观察到，在 rs1800860A>G 基因型中，AG 与疾病风险增加无关（OR 95%CI=0.568[0.238-1.356]），而 GG 基因型与疾病风险增加相关（OR 95%CI=2.278[0.967-5.366]）。在 rs1800861G>T 基因型中，GT 与降低疾病风险相关（OR 95%CI=0.230[0.0981-0.539]），而 TT 基因型与疾病风险增加相关（OR 95%CI=9.647[3.830-24.302]）。通过 Fisher 确切检验比较 rs1800861G>T 中 GT 和 TT 的基因型分布在短段疾病（SSD）病例和长段疾病（LSD）和全结肠无神经节细胞症之间的差异，具有统计学意义（P=0.0476 和 0.0054）。
本研究结果支持 RET 通路的变异可能在 HSCR 的发生发展中起重要作用的假设。
