Higher G allele frequency of RET C2307t>G polymorphism in female patients with Hirschsprung disease in Yogyakarta, Indonesia
AbstractBackground Hirschsprung disease (HSCR) is a heterogenous
congenital disorder and the current research show that the RET
gene is a major locus involved in its pathogenesis. However,
whether these genes take a part in sporadically Indonesian HSCR
have not been fully understood.
Objective The aim of this study was to analyze the association of
RET gene c2307T>G polymorphism among HSCR patient in
Methods Genomic DNA was extracted from bowel tissues of 34
patients with sporadic HSCR which were removed by surgery as
case group and blood DNA from 46 healthy persons as control
group without history of genetic disorder. Exon 13 of RET gene
was amplified by polymerase chain reaction (PCR) and was
analyzed by restriction fragment length polymorphism (RFLP).
Results Of 34 patients, 22 were males and 12 were females, giving
male to female ratio of 1.83:1. The c2307T>G polymorphism in
RET exon 13 was not significantly difference between patient
and control group (chi-square test P=0.17). However, there was
a significant difference in female patient compare with control
(chi-square test P=0,04).
Conclusion The RET gene c2307T>G polymorphism was found
among HSCR patient in Yogyakarta population. This poly-
morphism can be used as predictor for development of HSCR
among female individual.
syndromes, and genetics: a review. J Med Genet 2001;38:729â€“
2. Ceccherini I, Hofstra R, Luo Y, Stulp RP, Barone V, Stelwagen
T, et al. DNA polymorphisms and conditions for SSCP
analysis of the 20 exons of the RET protooncogene.
3. Kusafuka T, Puri P. Genetic aspects of Hirschsprungâ€™s disease.
Semin Pediatr Surg 1998; 7:148â€“55.
4. Gath R, Goessling A, Keller KM, Koletzko S, Coerdt W,
Muntefering H, et al. Analysis of the RET, GDNF, EDN3,
and EDNRB genes in patients with intestinal neuronal
dysplasia and Hirschsprung disease. Gut 2001;48:671â€“5.
5. Garcia-Barcelo MM, Sham MH, Lui VC, Chen BL, Song
YQ, Lee WS, et al. Chinese patients with sporadic
Hirschsprungâ€™s disease are predominantly represented by a
single RET haplotype. J Med Genet 2006;40:122.
6. Lesueur F, Corbex M, McKay JD, Lima J, Soares P, Griseri P,
et al. Specific haplotypes of the RET proto-oncogene are over-
represented in patients with sporadic papillary thyroid
carcinoma. J Med Genet 2002;39;260-5.
7. Griseri P, Sancandi M, Patrone G, Bocciardi R, Hofstra R,
Ravazzolo R, et al. A single-nucleotide polymorphic variant
of the RET protooncogene is underrepresented in sporadic
Hirschsprung disease. Eur J Hum Genet 2000; 8:721â€“4.
8. Sancandi M, Griseri P, Pesce B, Patrone G, Puppo F, Lerone
M, et al. Single nucleotide polymorphic alleles in the 5â€™ region
of the RET proto-oncogene define a risk haplotype in
Hirschsprungâ€™s disease. J Med Genet 2003; 40:714â€“8.
9. Wu TT, Tsai TW, Chu CT, Lee ZF, Hung CM, Su CC, et al.
Low RET mutation frequency and polymorphism analysis of
the RET and EDNRB genes in patients with Hirschsprung
disease in Taiwan. J Hum Genet 2005; 50:168â€“174.
10. Sangkhathat S, Kusafuka T, Chengkriwate P, Patrapinyokul
S, Sangthong B, Fukuzawa M. Mutations and polymorphisms
of Hirschsprung disease candidate genes in Thai patients. J
Hum Genet 2006;51:1126â€“32.
11. Fitze G, Schreiber M, Kuhlisch E, Schackert HK, Roesner D.
Association of RET protooncogene codon 45 polymorphism with
Hirschsprung disease. Am J Hum Genet 1999;65:1469â€“73.
12. Lantieri F, Griseri P, Puppo F, Campus R, Martucciello G,
Ravazzolo R, et al. Haplotypes of the Human RET proto-
oncogene associated with Hirschsprung disease in the Italian
population derive from a single ancestral combination of
Alleles. Annals of Hum Genet 2005;70:12â€“26.
13. Borrego S, Saez ME, Ruiz A, Gimm O, Lopez-Alonso M,
Antinolo G, et al. Specific polymorphisms in the RET
protooncogene are over-represented in patients with
Hirschsprung disease and may represent loci modifying
phenotypic expression. J Med Genet 1999; 36:771-4.
14. Smigiel R, Lebioda A, Patkowski D, Czernik J, Dobosz T,
Pesz K, et al. Single nucleotide polymorphisms in the RET
gene and their correlations with Hirschsprung disease
phenotype. J Appl Genet 2006;47:261â€“7.
15. Sakai T, Nirasawa Y, Itoh Y, Wakizaka A. Japanese patients
with sporadic Hirschsprung: mutation analysis of the receptor
tyrosine kinase proto-oncogene, endothelin-B receptor,
endothelin-3, glial cell line-derived neurotrophic factor and
neurturin genes: a comparison with similar studies. Eur J
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.