Is there a link between the calcium sensing receptor and Hirschsprung's disease? A mutational analysis

被引:0
|
作者
Romero, Philipp [1 ]
Niesler, Beate [2 ]
Schmitz-Winnenthal, Hubertus [3 ]
Fitze, Guido [4 ]
Holland-Cunz, Stefan
机构
[1] Univ Heidelberg, Chirurg Klin, Sekt Kinderchirurg, Dept Surg,Div Pediat Surg, D-69120 Heidelberg, Germany
[2] Univ Heidelberg, Dept Human Mol Genet, D-69120 Heidelberg, Germany
[3] Univ Heidelberg, German Canc Ctr, D-69120 Heidelberg, Germany
[4] Univ Dresden, Dept Pediat Surg, D-01307 Dresden, Germany
关键词
Hirschsprung's disease; Genetics; Calcium sensing receptor; Mutation; Polymorphism; EXTRACELLULAR CA2+-SENSING RECEPTOR; GASTROINTESTINAL-TRACT; R990G POLYMORPHISM; ROLES; HYPERCALCIURIA; GENE;
D O I
10.1016/j.jpedsurg.2011.10.010
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Introduction: Hirschsprung's disease (HD) is a congenital malformation of the hindgut characterized by the absence of enteric ganglion cells in the submucosal and myenteric plexuses. Hirschsprung's disease is routinely treated by resection of the aganglionic bowel and pull-through procedure of the proximal ganglionated bowel to the anorectal region. Occasionally, after resection of the aganglionic bowel, HD patients still experience persistent disturbances in gut motility. The etiology of HD as well as the underlying pathomechanism for postoperative disturbances in gut motility is unclear. Molecular analysis of putative candidate genes may help to clarify the pathophysiology of these conditions. In the present study, we investigated the correlation between mutations and polymorphisms in the calcium sensing receptor (CaSR) and HD patients. Methods: Mutational screening of the CaSR coding sequence was performed via polymerase chain reaction and direct sequencing of the amplified samples from 63 HD patients and 100 controls. Results: We identified 3 common polymorphisms (p.A986S, p.G990R, and p.Q1011E) residing in exon 7 and 1 polymorphismin intron 5 (IVS 5-88 T>C) of the CaSR gene. Overall, 16 patients (25%) and 25 controls (25%) were carriers of the p. A986S polymorphism (P = 1). The incidence of p. R990G polymorphism of patients was twice as high as in the control group (P = .17). Furthermore, we verified a 4 times higher incidence of p. Q1011E polymorphism carriers in patients compared to the control group (P = .1). Conclusion: We found a higher incidence of R990G and Q1011E polymorphisms in HD patients compared to controls. However, there was no statistically significant association between HD and the 3 polymorphic variants in the intracellular signaling region of CaSR. It will be important to further investigate genetic variations in CaSR in more patient cohorts to better characterize the function of this gene and to establish a correlation between CaSR variants and HD. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:551 / 555
页数:5
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