RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F14%3A10296215" target="_blank" >RIV/00064203:_____/14:10296215 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/14:10293043 RIV/00023761:_____/14:#0000480 RIV/00064203:_____/14:10293043

Result on the web

<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045806/" target="_blank" >http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045806/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0098957" target="_blank" >10.1371/journal.pone.0098957</a>

Result language

angličtina

Original language name

RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease

Original language description

Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene&apos;s single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p,0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire RET proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/NT13901" target="_blank" >NT13901: Study of the Genetic Alterations in Thyroid Cancer</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2014

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS One

ISSN

1932-6203

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

1-9

UT code for WoS article

000338430700102

EID of the result in the Scopus database

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