Association of HLA-DRB1*04 gene with Hashimoto’s thyroiditis among Iraqi-Kurdish population in Erbil province

Bakhtawar Ziad Omer
Department of Medical Microbiology, College of Health Sciences, Hawler Medical University, Erbil, Iraq.
Sahar Mohammed Zaki Abdullah
Department of Medical Microbiology, College of Health Sciences, Hawler Medical University, Erbil, Iraq.
Share:

Abstract

Background and objective: Hashimoto’s thyroiditis is one of the common autoimmune thyroid diseases with increasing incidence in the general population. It has been suggested that a combination of genetic and environmental factors increase the risk of developing the disease. The current study aimed to find the association between HLA-DRB1*04 gene with Hashimoto's Thyroiditis among the Iraqi-Kurdish population in Erbil Province.

Methods: The case-control study was conducted on 45 untreated patients with Hashimoto’s thyroiditis who have already been diagnosed and 45 control subjects. Blood specimens were taken from the subjects for gene detection purposes via conventional polymerase chain reaction. Sera specimens were used to run enzyme linked immunosorbent assay to measure the level of IFNγ.

Results: The age of subjects ranged from 32 to 63 years with no significant difference between mean ±SE of cases (46.822±1.087 years) with the mean ±SE (47.044 ±1.162 years) of the control subjects (P = 0.999). The mean ±SE of free T3 and T4 levels was lower in cases in comparison to those of controls, while the mean ±SE of TSH level in cases was significantly higher compared to those of controls. Statistically there was a highly significant difference in the mean ±SE of free T3, free T4 and TSH levels between cases and controls (P <0.001). Furthermore, the mean ±SE of anti-TPO, anti-Tg and IFNγ levels was higher in cases compared to those of control subjects. Statistical analysis shows a highly significant difference between mean ±SE of anti-TPO and anti-Tg antibody levels of cases compared to those of controls (P <0.001). As for IFNγ level, there was a significant difference between mean±SE of IFNγ levels in cases and controls (P = 0.021). The conventional polymerase chain reaction results showed that 39/45 (86.7%) of cases were tested positive for HLA-DRB1*04, while only 20/45 (44.04 %) of the control subjects tested positive for the gene, statistical analysis revealed a highly significant association between the existence of the gene with HT disease (P <0.001).

Conclusion: The study revealed a highly significant association between the existence of HLA-DRB1*04 gene and Hashimoto's thyroiditis disease among the Iraqi-Kurdish population in Erbil Province.

Metrics

Metrics Loading ...

References

  1. Caturegli P, De Remigis A, Chuang K, Dembele M, Iwama A, Iwama S. Hashimoto's thyroiditis: celebrating the centennial through the lens of the Johns Hopkins hospital surgical pathology records. J Thyroid Res. 2013; 23(2):142–50. https://doi:org/10.1089/thy.2012.0554
  2. Baretić M. [100 years of Hashimoto thyroiditis, still an intriguing disease]. Acta Med Croatica. 2011; 65(5):453–7.
  3. Ralli M, Angeletti D, Fiore M, D'Aguanno V, Lambiase A, Artico M, et al. Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. J Autoimmunity Reviews. 2020:102649. https://doi.org/10.1016/j.autrev.2020.102649
  4. Ajjan RA, Weetman AP. The pathogenesis of Hashimoto’s thyroiditis: further developments in our understanding. Horm Metab Res. 2015; 47(10):702–10. https://doi.org/10.1055/s-0035-1548832
  5. Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. J Autoimmunity Reviews. 2015; 14(2):174–80. https://doi.org/10.1016/j.autrev.2014.10.016
  6. Zaletel K, Gaberšček S. Hashimoto's Thyroiditis: From Genes to the Disease. Curr Genomics. 2011; 12(8):576-88. https://doi.org/10.2174%2F138920211798120763
  7. Doniach D, Roitt IM. Auto-immunity in Hashimoto's disease and its implications. J Clin Endocrinol Metab. 1957; 17(11):1293–304. https://doi.org/10.1210/jcem-17-11-1293
  8. Fröhlich E, Wahl R. Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases. Front Immunol. 2017; 8:52. https://doi.org/10.3389/fimmu.2017.00521
  9. Brčić L, Barić A, Gračan S, Torlak V, Brekalo M, Škrabić V, et al. Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis. Sci Rep. 2019; 9(1):5360. https://doi.org/10.1038/s41598-019-41850-6
  10. Radetti G. Clinical aspects of Hashimoto's thyroiditis. Endocr Dev. 2014; 26:158–70. https://doi.org/10.1159/000363162
  11. Higgins V, Patel K, Kulasingam V, Beriault D, Rutledge A, Selvaratnam R. Analytical performance evaluation of thyroid-stimulating hormone receptor antibody (TRAb) immunoassays. Clin Biochem. 2020; 86:56–60. https://doi.org/10.1016/j.clinbiochem.2020.08.007
  12. Ma S, Wu J, Wu J, Wei Y, Zhang L, Ning Q, et al. Relationship between HLA-DRB1 allele polymorphisms and familial aggregations of hepatocellular carcinoma. Curr Oncol. 2016; 23(1):e1–7. https://doi.org/10.3747/co.23.2839
  13. Al-Hashimi AM. Thyroid Nodules in Baghdad, Iraq: A Personal Experience. Int J Sci Res. 2015; 4(7):588–9.
  14. Pyzik A, Grywalska E, Matyjaszek-Matuszek B, Roliński J. Immune disorders in Hashimoto's thyroiditis: what do we know so far? J Immunol Res. 2015; 2015:979167. https://doi.org/10.1155/2015/979167
  15. Desai MK, Brinton RD. Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan. Front Endocrinol (Lausanne). 2019; 10:265. https://doi.org/10.3389%2Ffendo.2019.00265
  16. AngumF, Khan T, Kaler J, Siddiqui L, Hussain A. The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus. 2020; 12(5):e8094. https://doi.org/10.7759/cureus.8094
  17. Siriweera EH, Ratnatunga NV. Profile of Hashimoto's Thyroiditis in Sri Lankans: Is There an Increased Risk of Ancillary Pathologies in Hashimoto's Thyroiditis? J Thyroid Res. 2010; 2010:124264. https://doi.org/10.4061/2010/124264
  18. de Freitas CU, Grimaldi Campos RA, Rodrigues Silva MAF, Panachão MRI, de Moraes JC, Waissmann W, et al. Can living in the surroundings of a petrochemical complex be a risk factor for autoimmune thyroid disease?Environ. 2010; 110(1):112–7. https://doi.org/10.1016/j.envres.2009.10.009
  19. Kust D, Matesa N. The impact of familial predisposition on the development of Hashimoto's thyroiditis. Acta Clin Belg. 2020; 75(2):104–8. https://doi.org/10.1080/ 17843286.2018.1555115
  20. Kawasaki M, Ito M, Danno H, Kousaka K, Nakamura T, Yoshioka W, et al. The association between thyroid hormone balance and thyroid volume in patients with Hashimoto thyroiditis. Endocr J. 2019; 66(9):763–8.https://doi.org/10.1507/endocrj.ej19-0063
  21. Abdullah YJ, Essa RH, Jumaa MG. Association of Hashimotoʼs Thyroiditis with IRGM Snps (Rs13361189 T/C, Rs4958847 G/A, And Rs10065172 C/T) In Iraqi Arab Patients. Nveo. 2021:5441–53.
  22. Álvarez-Sierra D, Marín-Sánchez A, Ruiz-Blázquez P, de Jesús Gil C, Iglesias-Felip C, González Ó, et al. Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: Insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity. J Autoimmun. 2019; 103:102285. https://doi.org/10.1016/j.jaut.2019.05.013
  23. Bossowski A, Harasymczuk J, Moniuszko A, Bossowska A, Hilczer M, Ratomski K. Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases. J Thyroid Res. 2011; 4(1):13. https://doi.org/10.1186/1756-6614-4-13
  24. Tomer Y. Hepatitis C and interferon induced thyroiditis. J Autoimmun. 2010; 34(3):J322–6. https://doi.org/10.1016/j.jaut.2009.11.008
  25. Wysocki T, Olesińska M, Paradowska-Gorycka A. Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis-From Research to Clinical Practice. Cells. 2020; 9(5). https://doi.org/10.3390/cells9051127
  26. Scally SW, Petersen J, Law SC, Dudek NL, Nel HJ, Loh KL, et al. A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J Exp Med. 2013; 210(12):2569–82. https://doi.org/10.1084/jem.20131241
  27. Tobón GJ, Youinou P, Saraux A. The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis. J Autoimmun. 2010; 35(1):10–4. https://doi.org/10.1016/j.jaut.2009.12.009
  28. Matzaraki V, Kumar V, Wijmenga C, Zhernakova A. The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biol. 2017. 18; 76. https://doi.org/10.1186/s13059-017-1207-1
  29. Kokaraki G, Daniilidis M, Yiangou M, Arsenakis M, Karyotis N, Tsilipakou M, et al. Major histocompatibility complex class II (DRB1*, DQA1*, and DQB1*) and DRB1*04 subtypes' associations of Hashimoto's thyroiditis in a Greek population. Tissue Antigens. 2009; 73(3):199–205. https://doi.org/10.1111/j.1399-0039.2008.01182.x
  30. Ramgopal S, Rathika C, Padma MR, Murali V, Arun K, Kamaludeen MN, et al. Interaction of HLA-DRB1* alleles and CTLA4 (+49 AG) gene polymorphism in Autoimmune Thyroid Disease. Gene. 2018; 642:430–8. https://doi.org/10.1016/j.gene.2017.11.057
  31. Cho WK, Jung MH, Choi EJ, Choi HB, Kim TG, Suh BK. Association of HLA alleles with autoimmune thyroid disease in Korean children. Horm Res Paediatr. 2011; 76(5):328–34. https://doi.org/10.1159/000331134
  32. Petrone A, Giorgi G, Mesturino CA, Capizzi M, Cascino I, Nistico L, et al. Association of DRB1*04-DQB1*0301 haplotype and lack of association of two polymorphic sites at CTLA-4 gene with Hashimoto's thyroiditis in an Italian population. Thyroid. 2001; 11(2):171–5. https://doi.org/10.1089/105072501300042901
  33. Zeitlin AA, Heward JM, Newby PR, Carr-Smith JD, Franklyn JA, Gough SCL, et al. Analysis of HLA class II genes in Hashimoto's thyroiditis reveals differences compared to Graves’ disease. Genes & Immunity. 2008; 9(4):358–63. https://doi.org/10.1038/gene.2008.26
  34. Ueda S, Oryoji D, Yamamoto K, Noh JY, Okamura K, Noda M, et al. Identification of independent susceptible and protective HLA alleles in Japanese autoimmune thyroid disease and their epistasis. J Clin Endocrinol Metab. 2014; 99(2):E379–83. https://doi.org/10.1210/jc.2013-2841
How to Cite
Ziad Omer, B. ., & Mohammed Zaki Abdullah, S. . (2023). Association of HLA-DRB1*04 gene with Hashimoto’s thyroiditis among Iraqi-Kurdish population in Erbil province. Zanco Journal of Medical Sciences (Zanco J Med Sci), 27(2), 184–193. https://doi.org/10.15218/zjms.2023.021

Send mail to Author


Send Cancel