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Hum Genomics. 2016 Oct 24;10(1):34.

Novel genetic risk variants for pediatric celiac disease.

Author information

1
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece.
2
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
3
Complete Genomics Inc., Mountain View, CA, USA.
4
BGI Shenzhen, Shenzhen, 51803, China.
5
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
6
Department of Immunology and Histocompatibility, "Aghia Sophia" Children's Hospital, Athens, Greece.
7
First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, Athens, Greece.
8
Department of Gastroenterology and Nutrition, University Children's Hospital, Medical Faculty, University of Belgrade, Belgrade, Serbia.
9
Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta.
10
Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, 265 04, Patras, Greece. thkatsila@upatras.gr.

Abstract

BACKGROUND:

Celiac disease is a complex chronic immune-mediated disorder of the small intestine. Today, the pathobiology of the disease is unclear, perplexing differential diagnosis, patient stratification, and decision-making in the clinic.

METHODS:

Herein, we adopted a next-generation sequencing approach in a celiac disease trio of Greek descent to identify all genomic variants with the potential of celiac disease predisposition.

RESULTS:

Analysis revealed six genomic variants of prime interest: SLC9A4 c.1919G>A, KIAA1109 c.2933T>C and c.4268_4269delCCinsTA, HoxB6 c.668C>A, HoxD12 c.418G>A, and NCK2 c.745_746delAAinsG, from which NCK2 c.745_746delAAinsG is novel. Data validation in pediatric celiac disease patients of Greek (n = 109) and Serbian (n = 73) descent and their healthy counterparts (n = 111 and n = 32, respectively) indicated that HoxD12 c.418G>A is more prevalent in celiac disease patients in the Serbian population (P < 0.01), while NCK2 c.745_746delAAinsG is less prevalent in celiac disease patients rather than healthy individuals of Greek descent (P = 0.03). SLC9A4 c.1919G>A and KIAA1109 c.2933T>C and c.4268_4269delCCinsTA were more abundant in patients; nevertheless, they failed to show statistical significance.

CONCLUSIONS:

The next-generation sequencing-based family genomics approach described herein may serve as a paradigm towards the identification of novel functional variants with the aim of understanding complex disease pathobiology.

KEYWORDS:

Celiac disease; Disease predisposition; Family genomics; Genomic variants; Next-generation sequencing

PMID:
27836013
PMCID:
PMC5105295
DOI:
10.1186/s40246-016-0091-1
[Indexed for MEDLINE]
Free PMC Article

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