TY - JOUR
TI - Novel genetic risk variants for pediatric celiac disease
AU - Balasopoulou, A.
AU - Stanković, B.
AU - Panagiotara, A.
AU - Nikčevic, G.
AU - Peters, B.A.
AU - John, A.
AU - Mendrinou, E.
AU - Stratopoulos, A.
AU - Legaki, A.I.
AU - Stathakopoulou, V.
AU - Tsolia, A.
AU - Govaris, N.
AU - Govari, S.
AU - Zagoriti, Z.
AU - Poulas, K.
AU - Kanariou, M.
AU - Constantinidou, N.
AU - Krini, M.
AU - Spanou, K.
AU - Radlovic, N.
AU - Ali, B.R.
AU - Borg, J.
AU - Drmanac, R.
AU - Chrousos, G.
AU - Pavlovic, S.
AU - Roma, E.
AU - Zukic, B.
AU - Patrinos, G.P.
AU - Katsila, T.
JO - Human Genome Variation
PY - 2016
VL - 10
TODO - 1
SP - null
PB - BioMed Central Ltd.
SN - 2054-345X
TODO - 10.1186/s40246-016-0091-1
TODO - genomic DNA;  immunoglobulin A;  integrin;  interleukin 2;  interleukin 21;  microRNA;  protein glutamine gamma glutamyltransferase 2, Article;  bioinformatics;  celiac disease;  cell adhesion;  cell motility;  clinical article;  controlled study;  DNA isolation;  endothelium cell;  gene;  gene frequency;  gene replication;  genetic analysis;  genetic predisposition;  genetic risk;  genetic susceptibility;  genetic variability;  genomics;  Greece;  HoxB6 gene;  HoxD12 gene;  human;  KIAA1109 gene;  NCK2 gene;  next generation sequencing;  protein structure;  Serbian (citizen);  single nucleotide polymorphism;  SLC9A4 gene;  binding site;  celiac disease;  child;  genetic association study;  genetics;  high throughput sequencing;  molecular model;  mutation;  risk factor, Binding Sites;  Celiac Disease;  Child;  Gene Frequency;  Genetic Association Studies;  Genetic Predisposition to Disease;  High-Throughput Nucleotide Sequencing;  Humans;  Models, Molecular;  Mutation;  Polymorphism, Single Nucleotide;  Risk Factors
TODO - 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. © 2016 The Author(s).
ER -