학술논문
HLA-DQB1 Position 57 Defines Susceptibility to Isolated and Polyglandular Autoimmunity in Adults: Interaction With Gender
CLINICAL RESEARCH ARTICLE
CLINICAL RESEARCH ARTICLE
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. June 2019, Vol. 104 Issue 6, p1907, 10 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Endocrine autoimmune diseases are associated with distinct genetic profile of the HLA governing the T cell response to self-antigens. Susceptibility to type 1 diabetes (T1D) (1, 2), Addison disease (AD) [...]
Context: Autoimmune endocrinopathies result from environmental triggers on the genetic background of risk alleles, especially HLA-DR and HLA-DQ with alanine (Ala) in HLA-DQB1 position 57 ([Ala.sup.57]), whereas amino acid [Asp.sup.57] is protective. Objectives: Differentiate the effects of HLA-DQB1 amino acid variants at position 57 in adult patients with isolated endocrinopathies and autoimmune polyglandular syndrome type 2 (APS-2) compared with healthy controls in relation to gender. Setting: University Hospital Frankfurt, Frankfurt, Germany. Participants: Two hundred seventy-eight patients with APS-2 and 1373 patients with isolated endocrinopathies: [type 1 diabetes (T1D), n = 867], Addison disease (AD, n = 185), autoimmune thyroiditis (AIT, n = 321) and 526 healthy controls. Results: Homozygous HLA-DQB1 [Ala.sup.57] was more frequent in polyglandular T1D/AIT (OR 11.7, [P.sub.c] = 3 X [10.sup.7]) and AD/AIT (OR 4.0, [P.sub.c] =3 X [10.sup.7]), as well as in isolated T1D (OR 9.7, [P.sub.c] = 3 X [10.sup.7]) and AD (OR 3.1, [P.sub.c] =3 X [10.sup.7]). Heterozygous HLA-DQB1 57 Ala/non-Ala was increased in women with isolated AD and polyglandular AD/AIT (both OR 1.7, [P.sub.c] = 0.02) whereas the same amino acid variant was overrepresented in men with T1D compared with women (OR 1.6, [P.sub.c] = 0.004). The amino acid [Ala.sup.57] was more frequent (OR 2.0, [P.sub.c] = 0.02) and the amino acid [Asp.sup.57] was much more rare (OR 0.4, [P.sub.c] = 0.007) in the APS-2 cohort T1D/AIT than in AD/AIT. Conclusion: HLA-DQB1 confers strong susceptibility by [Ala.sup.57] homozygosity and protection by non-[Ala.sup.57], both in adult isolated and polyglandular diseases. Frequencies of HLA-DQB1 amino acids differentiate between APS-2 T1D/AIT and AD/AIT. HLA-DQB1 [Ala.sup.57] heterozygous women are at increased risk for AD or AIT, whereas men were found to have an increased susceptibility for T1D. (J Clin Endocrinol Metab 104: 1907-1916, 2019)
Context: Autoimmune endocrinopathies result from environmental triggers on the genetic background of risk alleles, especially HLA-DR and HLA-DQ with alanine (Ala) in HLA-DQB1 position 57 ([Ala.sup.57]), whereas amino acid [Asp.sup.57] is protective. Objectives: Differentiate the effects of HLA-DQB1 amino acid variants at position 57 in adult patients with isolated endocrinopathies and autoimmune polyglandular syndrome type 2 (APS-2) compared with healthy controls in relation to gender. Setting: University Hospital Frankfurt, Frankfurt, Germany. Participants: Two hundred seventy-eight patients with APS-2 and 1373 patients with isolated endocrinopathies: [type 1 diabetes (T1D), n = 867], Addison disease (AD, n = 185), autoimmune thyroiditis (AIT, n = 321) and 526 healthy controls. Results: Homozygous HLA-DQB1 [Ala.sup.57] was more frequent in polyglandular T1D/AIT (OR 11.7, [P.sub.c] = 3 X [10.sup.7]) and AD/AIT (OR 4.0, [P.sub.c] =3 X [10.sup.7]), as well as in isolated T1D (OR 9.7, [P.sub.c] = 3 X [10.sup.7]) and AD (OR 3.1, [P.sub.c] =3 X [10.sup.7]). Heterozygous HLA-DQB1 57 Ala/non-Ala was increased in women with isolated AD and polyglandular AD/AIT (both OR 1.7, [P.sub.c] = 0.02) whereas the same amino acid variant was overrepresented in men with T1D compared with women (OR 1.6, [P.sub.c] = 0.004). The amino acid [Ala.sup.57] was more frequent (OR 2.0, [P.sub.c] = 0.02) and the amino acid [Asp.sup.57] was much more rare (OR 0.4, [P.sub.c] = 0.007) in the APS-2 cohort T1D/AIT than in AD/AIT. Conclusion: HLA-DQB1 confers strong susceptibility by [Ala.sup.57] homozygosity and protection by non-[Ala.sup.57], both in adult isolated and polyglandular diseases. Frequencies of HLA-DQB1 amino acids differentiate between APS-2 T1D/AIT and AD/AIT. HLA-DQB1 [Ala.sup.57] heterozygous women are at increased risk for AD or AIT, whereas men were found to have an increased susceptibility for T1D. (J Clin Endocrinol Metab 104: 1907-1916, 2019)