HLA-DR in Hashimoto

Agata Jabrocka-Hybel; Anna Skalniak; Jakub Pietkowski; Renata Turek-Jabrocka; Palina Vyhouskaya; Adrian Tsang; Katarzyna Lizis-Kolus; Grzegorz Sokolowski; Dorota Pach; Alicja Hubalewska-Dydejczyk

doi:10.1530/endoabs.37.GP.26.10

GP.26.10

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Endocrine Abstracts (2015) 37 GP26.10 | DOI: 10.1530/endoabs.37.GP.26.10

ECE2015 Guided Posters Thyroid – hypothyroidism (10 abstracts)

HLA-DR in Hashimoto's thyroiditis

Agata Jabrocka-Hybel ^1, , Anna Skalniak ^1, , Jakub Piętkowski ^1, , Renata Turek-Jabrocka ^1, , Palina Vyhouskaya ¹ , Adrian Tsang ³ , Katarzyna Lizis-Kolus ⁴ , Grzegorz Sokołowski ² , Dorota Pach ^1, & Alicja Hubalewska-Dydejczyk ^1,

Err

Author affiliations

¹Jagiellonian University Medical College, Krakow, Poland; ²University Hospital in Krakow, Krakow, Poland; ³University of Ottawa, Ottawa, Ontario, Canada; ⁴Swietokrzyskie Oncology Centre, Kielce, Poland.

Background: The human leukocyte antigen (HLA) cluster is a genetic region that has been associated with multiple autoimmune disorders, also with autoimmune thyroid diseases. Plenty attempts to establish the significance of class II HLA-DR in Hashimoto’s thyroiditis (HT) development were undertaken in the past; however, reports are rather divergent. This might be caused by different criteria used to diagnose HT. There is however an alternative hypothesis, according to which a specific amino acid signature in the binding cleft, found among different types, might be more important in triggering susceptibility to HT than the type itself.

Aim: The presented study tests the hypothesis of whether and how HLA-DR can alter HT risk.

Materials and methods: Five hundred unrelated Hashimoto cases and healthy controls were studied. Including criteria for HT were in accordance with current recommendations (positive auto-antibodies, hypothyroidism, characteristic ultrasound). We sequenced the binding cleft-encoding exon of HLA-DRB1 in all participants. For differences of allele frequencies between groups the χ² test was implemented. Stepwise logistic regression analysis was performed for testing the importance of amino acid signatures of the binding cleft.

Results and conclusions: We show results for HLA-DR of a big project on the genetics of HT. We found that, indeed, the amino acid signature of the binding cleft, encompassing positions 26, 30, 70, 71, and 74, might be important for the development of the disease, but our results let us also conclude that this model would explain only about 5% of the susceptibility to HT. The results for HLA-DR may also differ when additional genetic and environmental factors are considered simultaneously. It therefore seems reasonable to include this genetic region into analyses encompassing multiple genes as well as non-genetic factors. This will be the next step of our ongoing project.

Disclosure: This work was supported by the Polish National Science Centre – grant number DEC-2011/01/B/NZ5/00337 and by the Polish Ministry of Science and Higher Education – grant number K/ZDS/003694.