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. 2022 Apr 15;11(8):2223.
doi: 10.3390/jcm11082223.

Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Marta Wysocka-Mincewicz  1 , Artur Groszek  1 , Filip Ambrozkiewicz  2   3 , Agnieszka Paziewska  4   5   6 , Michalina Dąbrowska  2 , Anna Rybak  7 , Ewa Konopka  8 , Agnieszka Ochocińska  9 , Natalia Żeber-Lubecka  2   4 , Jakub Karczmarski  2   5 , Joanna B Bierła  8 , Ilona Trojanowska  8 , Agnieszka Rogowska  4   10 , Jerzy Ostrowski  2   4 , Bożena Cukrowska  8
Affiliations

Combination of HLA-DQ2/-DQ8 Haplotypes and a Single MSH5 Gene Variant in a Polish Population of Patients with Type 1 Diabetes as a First Line Screening for Celiac Disease?

Marta Wysocka-Mincewicz et al. J Clin Med. .

Abstract

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group (n = 248) and healthy controls (n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700-0.7690) in comparison with 0.664 (95% CI: 0.632-0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

Keywords: HLA-DQ2 haplotype; HLA-DQ8 haplotype; MSH5 gene; celiac disease; genetic screening; type 1 diabetes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Receiver Operational Characteristics (ROC) analysis presenting specificity and sensitivity of CD haplotypes (HLA-DQ2/HLA-DQ8), the rs3130484 variant of the MSH5 gene (MSH5), and a combination of MSH5 and HLA-DQ2/HLA-DQ8 (MSH5 + HLA-DQ2/HLA-DQ8) in the detection of CD in patients with T1D. Area under curve (AUC) for HLA-DQ2/HLA-DQ8 (DQ2/DQ8) = 0.664, 95% CI: 0.632–0.696; for MSH5 = 0.729, 95% CI: 0.694–0.763 for MSH5 + HLA DQ2/HLA DQ8 (MSH5 + DQ2/DQ8 = 0.735, 95% CI: 0.700–0.769).
See this image and copyright information in PMC

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