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J Clin Endocrinol Metab. 2018 Dec 5. doi: 10.1210/jc.2018-01974. [Epub ahead of print]

Gender Alters the MHC Class I HLA-A Association with Polyglandular Autoimmunity.

Author information

1
German Red Cross Blood Service West, Laboratory of Immunogenetics / HLA, Bad Kreuznach and Hagen, Germany.
2
Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany.
3
Molecular Thyroid Research Laboratory, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany.

Abstract

Context:

The Major Histocompatibility Complex (MHC) strongly contributes to the development of polyglandular autoimmunity (PGA).

Objective:

To evaluate the impact of gender on human leukocyte antigen (HLA) association with PGA for the first time.

Design:

Cross-sectional immunogenetic study.

Setting:

Academic, tertiary referral, orphan disease center for PGA (ORPHA 282196) and immunogenetics laboratory.

Subjects:

158 patients with coexistent type 1 diabetes and autoimmune thyroid disease (adult type three PGA, ORPHA 227982) and 479 unrelated healthy controls.

Methods:

All 637 Caucasian subjects were typed for HLA-A, -B, DRB1, -DQA1, and -DQB1 alleles at a two-field level.

Main outcome measure:

Modification of the gene-disease association by gender.

Results:

MHC class I HLA-A association was gender-related to both the total Caucasian adult type three PGA collective (n=158, p=0.0065) as well as in PGA patients with autoimmune Hashimoto's thyroiditis (n=91, p=0.010). Compared to HLA-A*02:01, A*11:01 was overrepresented in male patients, yet underrepresented in females (OR 1.49, 95% CI 0.55-3.88 vs. 0.42, 0.12-1.17). A*24:02 was underrepresented in males but not in female patients (OR 0.37, 95% CI 0.111.04 vs. 1.19, 0.65-2.15). Excluding the five most frequent alleles (A*01:01, A*02:01, A*03:01, A*11:01, and A*24:02), the sum of all other identified alleles was underrepresented in male patients (OR 0.37, 0.18-0.72, p=0.0046). The strong MHC HLA-B association with PGA (p<0.0001) was not gender-related (p=0.55). Further, no interaction with gender was observed for the MHC class II HLA-DRB1, DQA1, and DQB1 alleles.

Conclusion:

MHC class I HLA-A association with type three PGA is significantly affected by gender.

PMID:
30520966
DOI:
10.1210/jc.2018-01974

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