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Shared and unique common genetic determinants between pediatric and adult celiac disease

BACKGROUND: Based on age of presentation, celiac disease (CD) is categorised as pediatric CD and adult CD. It however remains unclear if these are genetically and/or phenotypically distinct disorders or just different spectrum of the same disease. We therefore explored the common genetic components...

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Autores principales: Senapati, Sabyasachi, Sood, Ajit, Midha, Vandana, Sood, Neena, Sharma, Suresh, Kumar, Lalit, Thelma, B. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957920/
https://www.ncbi.nlm.nih.gov/pubmed/27449795
http://dx.doi.org/10.1186/s12920-016-0211-8
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author Senapati, Sabyasachi
Sood, Ajit
Midha, Vandana
Sood, Neena
Sharma, Suresh
Kumar, Lalit
Thelma, B. K.
author_facet Senapati, Sabyasachi
Sood, Ajit
Midha, Vandana
Sood, Neena
Sharma, Suresh
Kumar, Lalit
Thelma, B. K.
author_sort Senapati, Sabyasachi
collection PubMed
description BACKGROUND: Based on age of presentation, celiac disease (CD) is categorised as pediatric CD and adult CD. It however remains unclear if these are genetically and/or phenotypically distinct disorders or just different spectrum of the same disease. We therefore explored the common genetic components underlying pediatric and adult CD in a well characterized north Indian cohort. METHODS: A retrospective analysis of children (n = 531) and adult (n = 871) patients with CD between January 2001 and December 2010 was done. The database included basic demographic characteristics, clinical presentations, associated diseases and complications, if any. The genotype dataset was acquired for children (n = 217) and adult CD patients (n = 340) and controls (n = 736) using Immunochip. Association analysis was performed using logistic regression model to identify susceptibility genetic variants. RESULTS: The predominant form of CD was classical CD in both pediatric and adult CD groups. There was remarkable similarity between pediatric and adult CD except for quantitative differences between the two groups such as female preponderance, non-classical presentation, co-occurrence of other autoimmune diseases being more common amongst adult CD. Notably, same HLA-DQ2 and –DQ8 haplotypes were established as the major risk factors in both types of CD. In addition, a few suggestively associated (p < 5 × 10(−4)) non-HLA markers were identified of which only ANK3 (rs4948256-A; rs10994257-T) was found to be shared and explain risk for ~45 % of CD patients with HLA allele. DISCUSSION: Overall phenotypic similarity between pediatric and adult CD groups can be explained by contribution of same HLA risk alleles. Different non-HLA genes/loci with minor risk seem to play crucial role in disease onset and extra intestinal manifestation of CD. None of the non-HLA risk variants reached genome-wide significance, however most of them were shown to have functional implication to disease pathogenesis. Functional relevance of our findings needs to be investigated to address clinical heterogeneity of CD. CONCLUSIONS: This present study is the first comparative study based on common genetic markers to suggest that CD in pediatric age group and in adults are the spectrum of the same disease with novel and shared genetic risk determinants. Follow-up fine mapping studies with larger study cohorts are warranted for further genetic investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-016-0211-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-49579202016-07-23 Shared and unique common genetic determinants between pediatric and adult celiac disease Senapati, Sabyasachi Sood, Ajit Midha, Vandana Sood, Neena Sharma, Suresh Kumar, Lalit Thelma, B. K. BMC Med Genomics Research Article BACKGROUND: Based on age of presentation, celiac disease (CD) is categorised as pediatric CD and adult CD. It however remains unclear if these are genetically and/or phenotypically distinct disorders or just different spectrum of the same disease. We therefore explored the common genetic components underlying pediatric and adult CD in a well characterized north Indian cohort. METHODS: A retrospective analysis of children (n = 531) and adult (n = 871) patients with CD between January 2001 and December 2010 was done. The database included basic demographic characteristics, clinical presentations, associated diseases and complications, if any. The genotype dataset was acquired for children (n = 217) and adult CD patients (n = 340) and controls (n = 736) using Immunochip. Association analysis was performed using logistic regression model to identify susceptibility genetic variants. RESULTS: The predominant form of CD was classical CD in both pediatric and adult CD groups. There was remarkable similarity between pediatric and adult CD except for quantitative differences between the two groups such as female preponderance, non-classical presentation, co-occurrence of other autoimmune diseases being more common amongst adult CD. Notably, same HLA-DQ2 and –DQ8 haplotypes were established as the major risk factors in both types of CD. In addition, a few suggestively associated (p < 5 × 10(−4)) non-HLA markers were identified of which only ANK3 (rs4948256-A; rs10994257-T) was found to be shared and explain risk for ~45 % of CD patients with HLA allele. DISCUSSION: Overall phenotypic similarity between pediatric and adult CD groups can be explained by contribution of same HLA risk alleles. Different non-HLA genes/loci with minor risk seem to play crucial role in disease onset and extra intestinal manifestation of CD. None of the non-HLA risk variants reached genome-wide significance, however most of them were shown to have functional implication to disease pathogenesis. Functional relevance of our findings needs to be investigated to address clinical heterogeneity of CD. CONCLUSIONS: This present study is the first comparative study based on common genetic markers to suggest that CD in pediatric age group and in adults are the spectrum of the same disease with novel and shared genetic risk determinants. Follow-up fine mapping studies with larger study cohorts are warranted for further genetic investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-016-0211-8) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-22 /pmc/articles/PMC4957920/ /pubmed/27449795 http://dx.doi.org/10.1186/s12920-016-0211-8 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Senapati, Sabyasachi
Sood, Ajit
Midha, Vandana
Sood, Neena
Sharma, Suresh
Kumar, Lalit
Thelma, B. K.
Shared and unique common genetic determinants between pediatric and adult celiac disease
title Shared and unique common genetic determinants between pediatric and adult celiac disease
title_full Shared and unique common genetic determinants between pediatric and adult celiac disease
title_fullStr Shared and unique common genetic determinants between pediatric and adult celiac disease
title_full_unstemmed Shared and unique common genetic determinants between pediatric and adult celiac disease
title_short Shared and unique common genetic determinants between pediatric and adult celiac disease
title_sort shared and unique common genetic determinants between pediatric and adult celiac disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957920/
https://www.ncbi.nlm.nih.gov/pubmed/27449795
http://dx.doi.org/10.1186/s12920-016-0211-8
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