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Autoimmunity. 2016 Jun;49(4):240-7. doi: 10.3109/08916934.2016.1164144. Epub 2016 Apr 20.

High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease.

Author information

1
a Department of Pediatric Endocrinology , Diabetes and Metabolic Diseases, UMC - University Children's Hospital , Ljubljana , Slovenia .
2
b Blood Transfusion Center of Slovenia, Tissue Typing Centre , Ljubljana , Slovenia .
3
c Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia , and.
4
d Department of Gastroenterology , Hepatology and Nutrition, UMC - University Children's Hospital , Ljubljana , Slovenia.

Abstract

Shared susceptibility alleles in the HLA region contribute to the co-existence of type 1 diabetes (T1D) and celiac disease (CD). The aim of our study was to identify HLA genotype variations that influence co-occurrence of T1D and CD (T1D + CD) and the order of their onset. Totally 244 patients, 67 with T1D, 68 with CD and 69 with T1D + CD, (split into "T1D first" and "CD first"), were analyzed. Control group consisted of 130 healthy unrelated individuals. Two-tailed Fisher's exact test was used for statistical analysis. The genetic background of Slovenian CD patients resembled more northern than southern European populations with DR3-DQ2/DR3-DQ2 (odds ratio [OR] = 19.68) conferring the highest risk. The T1D + CD was associated with DR3-DQ2/DR3-DQ2 (OR = 45.53) and even more with DR3-DQ2/DR4-DQ8 (OR = 93.76). DR3-DQ2/DR7-DQ2 played a neutral role in susceptibility for T1D + CD. The order of the onset of T1D or CD in patients with co-occurring diseases was not influenced by HLA risk genotype profile. DR3-DQ2/DR3-DQ2 was associated with an increased risk for developing CD in patients with T1D, whereas patients with CD carrying DR3-DQ2/DR4-DQ8 were at higher risk for developing T1D. In addition to other genetic factors including HLA class I alleles present on DR3-DQ2 extended haplotype, the second extended haplotype may moderate the risk for T1D + CD conferred by DR3-DQ2. Our results suggested that individuals carrying high-risk genotypes DR3-DQ2/DR3-DQ2 or DR3-DQ2/DR4-DQ8 would more likely develop both T1D and CD than either disease alone.

KEYWORDS:

Autoimmune diseases; Slovenian population; genetic susceptibility; major histocompatibility complex; order of onset

PMID:
27138053
DOI:
10.3109/08916934.2016.1164144
[Indexed for MEDLINE]

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