Association Between HLA-DRB1 Alleles and Gravesʼ Disease in Asian Populations: A Meta-Analysis

Abstract

Graves’ disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism. Genetic studies have shown that human leukocyte antigen (HLA) plays an important role in the development of GD. In this article, we performed a meta-analysis determined to evaluate the relationship between HLA-DRB1 alleles and GD. This meta-analysis included 9 studies (3582 cases in the case group and 23070 cases in the control group) and 27 alleles was performed. The combined results showed that, compared with the control group, GD patients have a significant increase in the frequency of DRB1*1403 (OR=2.50, 95% CI=1.78–3.51, pc<0.0001) and have a significant decrease in frequencies of DRB1* 0101 (OR=0.45, 95% CI=0.34–0.59, pc<0.0001) and DRB1*0701 (OR=0.44, 95% CI=0.35–0.55, pc<0.0001). The meta-analysis indicated that, in Asian populations, DRB1*1403 is a risk allele for GD, and DRB1*0101 and DRB1*0701 are protective against the occurrence of GD. We surprisingly discovered that the susceptibility alleles for GD in Asian populations are completely different from Caucasians and the protective alleles for GD in Asians are quite similar to those of Caucasians. The results of our study may provide new opportunities for gene-targeted therapy for GD in Asian populations.

Keywords

Gravesʼ disease - HLA-DRB1 alleles - Asians - meta-analysis

Publikationsverlauf

Eingereicht: 03. März 2024

Angenommen nach Revision: 24. März 2024

Artikel online veröffentlicht:
02. Mai 2024

• References

• 1 Davies TF, Andersen S, Latif R. et al. Graves' disease. Nat Rev Dis Primers 2020; 6: 52
• 2 Smith TJ, Hegedüs L. Graves' disease. N Engl J Med 2016; 375: 1552-1565
• 3 Tomer Y. Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics. Annu Rev of Pathol Mech Dis 2014; 9: 147-156
• 4 Dvornikova KA, Bystrova EY, Platonova ON. et al. Polymorphism of toll-like receptor genes and autoimmune endocrine diseases. Autoimm Rev 2020; 19: 102496
• 5 Brix TH, Kyvik KO, Christensen K. et al. Evidence for a major role of heredity in Graves' disease: a population-based study of two Danish twin cohorts. J Clin Endocrinol Metab 2001; 86: 930-934
• 6 McLeod DSA, Caturegli P, Cooper DS. et al. Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel. JAMA 2014; 311: 1563-1565
• 7 Shapira Y, Agmon-Levin N, Shoenfeld Y. Defining and analyzing geoepidemiology and human autoimmunity. J Autoimm 2010; 34: J168-J177
• 8 Shin D-H, Baek I-C, Kim HJ. et al. HLA alleles, especially amino-acid signatures of HLA-DPB1, might contribute to the molecular pathogenesis of early-onset autoimmune thyroid disease. PloS One 2019; 14: e0216941
• 9 Zawadzka-Starczewska K, Tymoniuk B, Stasiak B. et al. Actual associations between HLA haplotype and Graves' disease development. J Clin Med 2022; 11: 2492
• 10 Chen QY, Huang W, She JX. et al. HLA-DRB1*08, DRB1*03/DRB3*0101, and DRB3*0202 are susceptibility genes for Graves' disease in North American Caucasians, whereas DRB1*07 is protective. J Clin Endocrinol Metab 1999; 84: 3182-3186
• 11 Zeitlin AA, Heward JM, Newby PR. et al. Analysis of HLA class II genes in Hashimoto's thyroiditis reveals differences compared to Graves' disease. Gen. Immun 2008; 9: 358-363
• 12 Tomer Y, Davies TF. Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function. Endocrine Rev 2003; 24: 694-717
• 13 Jang HW, Shin HW, Cho H-J. et al. Identification of HLA-DRB1 alleles associated with Graves' disease in Koreans by sequence-based typing. Immunolog Invest 2011; 40: 172-182
• 14 Katahira M, Ogata H, Takashima H. et al. Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves' disease and Hashimoto's thyroiditis in the Japanese population. Hum Immunol 2021; 82: 26-231
• 15 Hashimoto K, Maruyama H, Nishiyama M. et al. Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population. Horm Res 2005; 64: 253-260
• 16 Park MH, Park YJ, Song EY. et al. Association of HLA-DR and -DQ genes with Graves disease in Koreans. Hum Immunol 2005; 66: 41-47
• 17 Huang S-M, Wu T-J, Lee TD. et al. The association of HLA -A, -B, and -DRB1 genotypes with Graves' disease in Taiwanese people. Tissue Antigen 2003; 61: 154-158
• 18 Ueda S, Oryoji D, Yamamoto K. et al. Identification of independent susceptible and protective HLA alleles in Japanese autoimmune thyroid disease and their epistasis. J Clin Endrocrinol Metab 2014; 99: E379-E383
• 19 Chu X, Yang M, Song Z-J. et al. Fine mapping MHC associations in Graves' disease and its clinical subtypes in Han Chinese. J Med Genet 2018; 55: 685-692
• 20 Chen P-L, Fann CS-J, Chu C-C. et al Comprehensive genotyping in two homogeneous Graves' disease samples reveals major and novel HLA association alleles. PloS One 2011; 6: e16635
• 21 Wongsurawat T, Nakkuntod J, Charoenwongse P. et al. The association between HLA class II haplotype with Graves' disease in Thai population. Tissue Antigen 2006; 67: 79-83
• 22 Muñoz-Ortiz J, Sierra-Cote MC, Zapata-Bravo E. et al. Prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in thyroid eye disease: a systematic review of the literature. System Rev 2020; 9: 201
• 23 Konno N, Yuri K, Taguchi H. et al. Screening for thyroid diseases in an iodine sufficient area with sensitive thyrotrophin assays, and serum thyroid autoantibody and urinary iodide determinations. Clin Endocrinol 1993; 38: 273-281
• 24 Sriphrapradang C, Pavarangkoon S, Jongjaroenprasert W. et al. Reference ranges of serum TSH, FT4 and thyroid autoantibodies in the Thai population: the national health examination survey. Clin Endocrinol 2014; 80: 751-756
• 25 Hollowell JG, Staehling NW, Flanders WD. et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87: 489-499
• 26 Bjoro T, Holmen J, Krüger O. et al. Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol 2000; 143: 639-647
• 27 O'Leary PC, Feddema PH, Michelangeli VP. et al. Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study. Clin Endocrinol 2006; 64: 97-104
• 28 Martin S, Dutescu MI, Sirbu A. et al. The clinical value of human leukocyte antigen HLA-DRB1 subtypes associated to Graves' disease in Romanian population. Immunol Invest 2014; 43: 479-490
• 29 Ban Y, Davies TF, Greenberg DA. et al. Arginine at position 74 of the HLA-DR beta1 chain is associated with Graves' disease Gene. Immun 2004; 5: 203-2088
• 30 Simmonds MJ, Howson JMM, Heward JM. et al Regression mapping of association between the human leukocyte antigen region and Graves disease. Am J Hum Genet 2005; 76: 157-163
• 31 Morris DL, Taylor KE, Fernando MMA. et al. Unraveling multiple MHC gene associations with systemic lupus erythematosus: model choice indicates a role for HLA alleles and non-HLA genes in Europeans. Am J Hum Genet 2012; 91: 778-793
• 32 Huang R, Yin J, Chen Y. et al. The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome. J Autoimmun 2015; 57: 53-59
• 33 Ji C, Liu S, Zhu K. et al. HLA-DRB1 polymorphisms and alopecia areata disease risk: A systematic review and meta-analysis. Medicine 2018; 97: e11790
• 34 Zamani M, Spaepen M, Bex M. et al. Primary role of the HLA class II DRB1*0301 allele in Graves disease. Am J Med Genet 2000; 95: 432-437
• 35 Jacobson EM, Huber A, Tomer Y. The HLA gene complex in thyroid autoimmunity: from epidemiology to etiology. J Autoimmun 2008; 30: 58-62
• 36 Gonzalez-Galarza FF, McCabe A, Santos Melo Dos EJ. et al. Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools. Nucl Acid Res 2020; 48: D783-D788
• 37 Barkia BS, Flesch BK, Hansen MP. et al. HLA class II differentiates between thyroid and polyglandular autoimmunity. Horm Meatb Res 2016; 48: 232-237
• 38 Okada Y, Momozawa Y, Ashikawa K. et al. Construction of a population-specific HLA imputation reference panel and its application to Graves' disease risk in Japanese. Nat Genet 2015; 47: 798-802
• 39 Menconi F, Monti MC, Greenberg DA. et al. Molecular amino acid signatures in the MHC class II peptide-binding pocket predispose to autoimmune thyroiditis in humans and in mice. Proc Natl Acad Sci U S A 2008; 105: 14034-14039
• 40 Hu X, Deutsch AJ, Lenz TL. et al. Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk. Nat Genet 2015; 47: 898-905
• 41 Gentil CA, Gammill HS, Luu CT. et al. Characterization of the HLA-DRβ1 third hypervariable region amino acid sequence according to charge and parental inheritance in systemic sclerosis. Arthr Res Ther 2017; 19: 46
• 42 Seo GH, Kim TH, Chung JH. Antithyroid drugs and congenital malformations: a nationwide Korean cohort study. Ann Intern Med 2018; 168: 405-413
• 43 Watanabe N, Narimatsu H, Noh JY. et al. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50, 385 patients with Graves' disease. J Clin Endocrinol Metab 2012; 97: E49-E53
• 44 Struja T, Fehlberg H, Kutz A. et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur J Endocrinol 2017; 176: 87-97
• 45 Li CW, Osman R, Menconi F. et al. Cepharanthine blocks TSH receptor peptide presentation by HLA-DR3: Therapeutic implications to Graves' disease. J Autoimmun 2020; 108: 102402