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. 2019 Mar 15;10(3):189-199.
doi: 10.4239/wjd.v10.i3.189.

Targeted genotyping for the prediction of celiac disease autoimmunity development in patients with type 1 diabetes and their family members

Maureen M Leonard  1 , Stephanie Camhi  1 , Victoria Kenyon  1 , Rebecca A Betensky  2 , Craig Sturgeon  1 , Shu Yan  1 , Alessio Fasano  1
Affiliations

Targeted genotyping for the prediction of celiac disease autoimmunity development in patients with type 1 diabetes and their family members

Maureen M Leonard et al. World J Diabetes. .

Abstract

Background: Patients with type 1 diabetes (T1D) and their first-degree relatives (FDRs) have an increased risk of developing celiac disease (CD) compared to the general population. This is largely explained by the shared association with major histocompatibility class II human leukocyte antigen (HLA) DQ2 and/or DQ8 between the two disease states.

Aim: To describe the frequency of CD autoimmunity (CDA) and the distribution of HLA and haptoglobin genotypes in patients with T1D and their FDRs. Additionally, we aimed at identifying predictors associated with an increased risk of developing CDA in patients with T1D and their family members.

Methods: We obtained clinical information and blood samples from 1027 participants (302 with T1D and 725 FDRs) over a five-year period. Samples were tested for autoantibodies associated with CD, HLA-DQ alleles, and haptoglobin genotype. We fit univariate and multiple logistic regression models for CDA separately for subjects with T1D and for FDRs of subjects with T1D.

Results: Implementation of a screening program increased the frequency of CDA by 2-fold in participants with T1D and 2.8-fold in their FDRs. Multivariate analysis found that, in participants with T1D, having both DR7-DQ2 and DR4-DQ8 was associated with an increased frequency of CDA. In FDRs of T1D patients, reported CD in the family was associated with an increased frequency of CDA during screening. Haptoglobin 2 genotype was not associated with developing CDA in the multivariate analysis.

Conclusion: Patients with T1D and their FDRs have a high frequency of CDA. Carrying both DR7-DQ2 and DR4-DQ8 was associated with development of CDA in patients with T1D.

Keywords: Coeliac; Diabetic; Gluten; Haptoglobin; Human leukocyte antigen; Screening.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare no conflict of interest.

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