ASSOCIATION BETWEEN PROINFLAMMATORY INTERLEUKIN-1 ß (IL1B) POLYMORPHISM AND HYPERTHYROIDISM IN IRAQI PATIENTS
Main Article Content
Keywords
Hyperthyroidism; Hormonal dysregulation; Interleukin-1β; Gene polymorphis
Abstract
This research examines the relationship between the proinflammatory interleukin-1β (IL1B) single nucleotide gene polymorphism and biochemical parameters in Iraqi hyperthyroid patients. A cohort comprising 220 individuals from Al-Hussein Teaching Hospital in Karbala, Iraq, participated in the study. Factors like smoking habits, residential location, hormone levels (TSH, T3, and T4), lipid profile (TG, TC, LDL, HDL, and VLDL) creatine kinase (CK), and glycemic indicators (HbA1c and FBS) were evaluated. IL1B-511 polymorphisms were detected through polymerase chain reaction (PCR) amplification and gel electrophoresis. Results highlighted a higher smoking prevalence among hyperthyroid patients. Significant differences were observed in T3, T4, and TSH levels between the patient and control groups (p ≤ 0.05), but not in FBS, HbA1c, CK, TC, LDL, HDL, and VLDL levels (p > 0.05). TG levels differed significantly, favoring the control group (p ≤ 0.05). The IL1B-511 CC genotype was notably linked to hyperthyroidism, with an odds ratio of 4.2 (95% CI: 1.19-14.74, p = 0.025). However, hormone concentrations (TSH, T3, T4) didn't significantly differ between C and T allele patients (p > 0.05). In conclusion, this study establishes a relationship between IL1B-511 polymorphism and hyperthyroidism in Iraqi patients. The results suggest the CC genotype of IL1B-511 might contribute to hyperthyroidism development.
References
[1] S. S. Ahmed and A. A. Mohammed, “Effects of thyroid dysfunction on hematological parameters: Case-controlled study,” Ann. Med. Surg., vol. 57, pp. 52–55, 2020, doi: 10.1016/j.amsu.2020.07.008.
[2] A. Kotwal et al., “Treatment of thyroid dysfunction and serum lipids: A systematic review and meta-analysis,” J. Clin. Endocrinol. Metab., vol. 105, no. 12, pp. 3683–3694, 2020, doi: 10.1210/clinem/dgaa672.
[3] B. Goichot, S. Bouée, C. Castello-Bridoux, and P. Caron, “Survey of Clinical Practice Patterns in the Management of 992 Hyperthyroid Patients in France,” Eur. Thyroid J., vol. 6, no. 3, pp. 152–159, 2017, doi: 10.1159/000453260.
[4] I. Strikić Đula et al., “Epidemiology of Hypothyroidism, Hyperthyroidism and Positive Thyroid Antibodies in the Croatian Population,” Biology (Basel)., vol. 11, no. 3, p. 394, 2022, doi: 10.3390/biology11030394.
[5] T. H. Brix, K. O. Kyvik, K. Christensen, and L. Hegedüs, “Evidence for a major role of heredity in Graves’ disease: A population-based study of two Danish twin cohorts,” J. Clin. Endocrinol. Metab., vol. 86, no. 2, pp. 930–934, 2001, doi: 10.1210/jc.86.2.930.
[6] M. J. Simmonds, “GWAS in autoimmune thyroid disease: Redefining our understanding of pathogenesis,” Nat. Rev. Endocrinol., vol. 9, no. 5, pp. 277–287, 2013, doi: 10.1038/nrendo.2013.56.
[7] X. Chu et al., “A genome-wide association study identifies two new risk loci for Graves’ disease,” Nat. Genet., vol. 43, no. 9, pp. 897–901, 2011, doi: 10.1038/ng.898.
[8] M. B. Leko, I. Gunjača, N. Pleić, and T. Zemunik, “Environmental factors affecting thyroid-stimulating hormone and thyroid hormone levels,” Int. J. Mol. Sci., vol. 22, no. 12, p. 6521, 2021, doi: 10.3390/ijms22126521.
[9] P. Fallahi et al., “Cytokines as Targets of Novel Therapies for Graves’ Ophthalmopathy,” Front. Endocrinol. (Lausanne)., vol. 12, p. 654473, 2021, doi: 10.3389/fendo.2021.654473.
[10] P. Behzadi et al., “The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs),” J. Immunol. Res., vol. 2022, 2022, doi: 10.1155/2022/2054431.
[11] K. Khazim, E. E. Azulay, B. Kristal, and I. Cohen, “Interleukin 1 gene polymorphism and susceptibility to disease,” Immunol. Rev., vol. 281, no. 1, pp. 40–56, 2018, doi: 10.1111/imr.12620.
[12] M. D. Turner, B. Nedjai, T. Hurst, and D. J. Pennington, “Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease,” Biochim. Biophys. Acta - Mol. Cell Res., vol. 1843, no. 11, pp. 2563–2582, 2014, doi: 10.1016/j.bbamcr.2014.05.014.
[13] J. Xu et al., “Systematic Review and Meta-Analysis on the Association between IL-1B Polymorphisms and Cancer Risk,” PLoS One, vol. 8, no. 5, p. e63654, 2013, doi: 10.1371/journal.pone.0063654.
[14] I. Gorący et al., “Polymorphism of interleukin 1b may modulate the risk of ischemic stroke in polish patients,” Med., vol. 55, no. 9, p. 558, 2019, doi: 10.3390/medicina55090558.
[15] M. Musker, J. Licinio, and M. L. Wong, “Inflammation genetics of depression,” in Inflammation and Immunity in Depression: Basic Science and Clinical Applications, Elsevier, 2018, pp. 411–425. doi: 10.1016/B978-0-12-811073-7.00023-4.
[16] M. A. Iddah et al., “Thryroid Hormones and Hematological Indices Levels in Thyroid Disorders Patients at Moi Teaching and Referral Hospital, Western Kenya,” Int. Sch. Res. Not., vol. 2013, 2013, doi: 10.1155/2013/385940.
[17] A. Dorgalaleh et al., “Effect of Thyroid Dysfunctions on Blood Cell Count and Red Blood Cell Indice,” Iran. J. Pediatr. Hematol. Oncol., vol. 3, no. 2, p. 73, 2013.
[18] X. Chen et al., “Relationship of gender and age on thyroid hormone parameters in a large Chinese population,” Arch. Endocrinol. Metab., vol. 64, pp. 52–58, 2019, doi: 10.20945/2359-3997000000179.
[19] P. N. Taylor et al., “Global epidemiology of hyperthyroidism and hypothyroidism,” Nat. Rev. Endocrinol., vol. 14, no. 5, pp. 301–316, 2018, doi: 10.1038/nrendo.2018.18.
[20] L. Bartalena, F. Bogazzi, M. L. Tanda, L. Manetti, E. Dell’Unto, and E. Martino, “Cigarette smoking and the thyroid,” Eur. J. Endocrinol., vol. 133, no. 5, pp. 507–512, 1995, doi: 10.1530/eje.0.1330507.
[21] K. Mann, “Risk of smoking in thyroid-associated orbitopathy.,” Exp. Clin. Endocrinol. Diabetes, vol. 107, no. S 05, pp. S164–S167, 1999, doi: 10.1055/s-0029-1212176.
[22] L. Hegedüs, T. H. Brix, and P. Vestergaard, “Relationship between cigarette smoking and Graves’ ophthalmopathy,” J. Endocrinol. Invest., vol. 27, pp. 256–271, 2004, doi: 10.1007/bf03345276.
[23] D. Kapoor and T. H. Jones, “Smoking and hormones in health and endocrine disorders,” Eur. J. Endocrinol., vol. 152, no. 4, pp. 491–499, 2005, doi: 10.1530/eje.1.01867.
[24] N.K. Kayumova, J.A. Nazarova, L.Kh. Mamadinova, I.A. Abbosova, & G.T. Abduvalieva. (2023). Assessment Of Quality Of Life And Cognitive Function In Patients With Primary Hypothyroidism. Journal of Population Therapeutics and Clinical Pharmacology, 30(14), 249–255. https://doi.org/10.47750/jptcp.2023.30.14.033
[25] T. Senturk, L. D. Kozaci, F. Kok, G. Kadikoylu, and Z. Bolaman, “Proinflammatory cytokine levels in hyperthyroidism,” Clin. Investig. Med., vol. 26, no. 2, pp. 58–63, 2003.
[26] Y. H. Juma’a and R. H. Allami, “The Association of TSHR Gene rs2268458 Polymorphism with Thyroid Disorders (Hyperthyroidism and Hypothyroidism) in a Sample of Iraqi Patients,” J. Forensic Med., vol. 15, no. 3, 2021, doi: 10.37506/ijfmt.v15i3.15509.
[27] X. Zhu and S. Y. Cheng, “New insights into regulation of lipid metabolism by thyroid hormone,” Curr. Opin. Endocrinol. Diabetes Obes., vol. 17, no. 5, pp. 408–413, 2010, doi: 10.1097/MED.0b013e32833d6d46.
[28] A. Ferdian, BSP. Pratondo, AP. Arifin, TR. Intansari, Y. Choiri, VC. Tansuri, A. Zahra, R. Ilmansyah, IGYP. Ananda and W. Pratiwi (2023) “Characteristics Of Patients with Grave’s Disease with ECG Sick Node Dysfunction (SND) With History of Thyroidectomy and PTU Treatment”, Journal of Population Therapeutics and Clinical Pharmacology, 30(13), pp. 80–97. doi: 10.47750/jptcp.2023.30.13.008.
[29] H. Nishitani, K. Okamura, S. Noguchi, K. Inoue, Y. Morotomi, and M. Fujishima, “Serum lipid levels in thyroid dysfunction with special reference to transient elevation during treatment in hyperthyroid graves’ disease,” Horm. Metab. Res., vol. 22, no. 9, pp. 490–493, 1990, doi: 10.1055/s-2007-1004953.
[30] A. W. C. Kung, R. W. C. Pang, I. Lauder, K. S. L. Lam, and E. D. Janus, “Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism,” Clin. Chem., vol. 41, no. 2, pp. 226–231, 1995, doi: 10.1093/clinchem/41.2.226.
[31] D. G. Yavuz, M. Yüksel, O. Deyneli, Y. Ozen, H. Aydin, and S. Akalin, “Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goiter patients,” Clin. Endocrinol. (Oxf)., vol. 61, no. 4, pp. 515–521, 2004, doi: 10.1111/j.1365-2265.2004.02123.x.
[32] M. Peppa, G. Betsi, and G. Dimitriadis, “Lipid Abnormalities and Cardiometabolic Risk in Patients with Overt and Subclinical Thyroid Disease,” J. Lipids, vol. 2011, pp. 1–9, 2011, doi: 10.1155/2011/575840.
[33] M. Kammoun-Krichen et al., “Association analysis of interleukin-1 gene polymorphisms in autoimmune thyroid diseases in the Tunisian population,” Eur. Cytokine Netw., vol. 18, no. 4, pp. 17–21, 2007, doi: 10.1684/ecn.2007.0104.
[34] K. Lacka et al., “Interleukin-1beta gene (IL-1beta) polymorphisms (SNP -511 and SNP +3953) in thyroid-associated ophthalmopathy (TAO) among the Polish population.,” Curr. Eye Res., vol. 34, no. 3, pp. 215–220, Mar. 2009, doi: 10.1080/02713680802699390.
[35] O. Khalilzadeh et al., “Graves’ ophthalmopathy and gene polymorphisms in interleukin-1α, interleukin-1β, interleukin-1 receptor and interleukin-1 receptor antagonist,” Clin. Exp. Ophthalmol., vol. 37, no. 6, pp. 614–619, 2009, doi: 10.1111/j.1442-9071.2009.02093.x.
[36] M. L. Chen, N. Liao, H. Zhao, J. Huang, and Z. F. Xie, “Association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and Graves’ disease risk: A meta-analysis of 11 case-control studies,” PLoS One, vol. 9, no. 1, p. e86077, 2014, doi: 10.1371/journal.pone.0086077.
[2] A. Kotwal et al., “Treatment of thyroid dysfunction and serum lipids: A systematic review and meta-analysis,” J. Clin. Endocrinol. Metab., vol. 105, no. 12, pp. 3683–3694, 2020, doi: 10.1210/clinem/dgaa672.
[3] B. Goichot, S. Bouée, C. Castello-Bridoux, and P. Caron, “Survey of Clinical Practice Patterns in the Management of 992 Hyperthyroid Patients in France,” Eur. Thyroid J., vol. 6, no. 3, pp. 152–159, 2017, doi: 10.1159/000453260.
[4] I. Strikić Đula et al., “Epidemiology of Hypothyroidism, Hyperthyroidism and Positive Thyroid Antibodies in the Croatian Population,” Biology (Basel)., vol. 11, no. 3, p. 394, 2022, doi: 10.3390/biology11030394.
[5] T. H. Brix, K. O. Kyvik, K. Christensen, and L. Hegedüs, “Evidence for a major role of heredity in Graves’ disease: A population-based study of two Danish twin cohorts,” J. Clin. Endocrinol. Metab., vol. 86, no. 2, pp. 930–934, 2001, doi: 10.1210/jc.86.2.930.
[6] M. J. Simmonds, “GWAS in autoimmune thyroid disease: Redefining our understanding of pathogenesis,” Nat. Rev. Endocrinol., vol. 9, no. 5, pp. 277–287, 2013, doi: 10.1038/nrendo.2013.56.
[7] X. Chu et al., “A genome-wide association study identifies two new risk loci for Graves’ disease,” Nat. Genet., vol. 43, no. 9, pp. 897–901, 2011, doi: 10.1038/ng.898.
[8] M. B. Leko, I. Gunjača, N. Pleić, and T. Zemunik, “Environmental factors affecting thyroid-stimulating hormone and thyroid hormone levels,” Int. J. Mol. Sci., vol. 22, no. 12, p. 6521, 2021, doi: 10.3390/ijms22126521.
[9] P. Fallahi et al., “Cytokines as Targets of Novel Therapies for Graves’ Ophthalmopathy,” Front. Endocrinol. (Lausanne)., vol. 12, p. 654473, 2021, doi: 10.3389/fendo.2021.654473.
[10] P. Behzadi et al., “The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs),” J. Immunol. Res., vol. 2022, 2022, doi: 10.1155/2022/2054431.
[11] K. Khazim, E. E. Azulay, B. Kristal, and I. Cohen, “Interleukin 1 gene polymorphism and susceptibility to disease,” Immunol. Rev., vol. 281, no. 1, pp. 40–56, 2018, doi: 10.1111/imr.12620.
[12] M. D. Turner, B. Nedjai, T. Hurst, and D. J. Pennington, “Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease,” Biochim. Biophys. Acta - Mol. Cell Res., vol. 1843, no. 11, pp. 2563–2582, 2014, doi: 10.1016/j.bbamcr.2014.05.014.
[13] J. Xu et al., “Systematic Review and Meta-Analysis on the Association between IL-1B Polymorphisms and Cancer Risk,” PLoS One, vol. 8, no. 5, p. e63654, 2013, doi: 10.1371/journal.pone.0063654.
[14] I. Gorący et al., “Polymorphism of interleukin 1b may modulate the risk of ischemic stroke in polish patients,” Med., vol. 55, no. 9, p. 558, 2019, doi: 10.3390/medicina55090558.
[15] M. Musker, J. Licinio, and M. L. Wong, “Inflammation genetics of depression,” in Inflammation and Immunity in Depression: Basic Science and Clinical Applications, Elsevier, 2018, pp. 411–425. doi: 10.1016/B978-0-12-811073-7.00023-4.
[16] M. A. Iddah et al., “Thryroid Hormones and Hematological Indices Levels in Thyroid Disorders Patients at Moi Teaching and Referral Hospital, Western Kenya,” Int. Sch. Res. Not., vol. 2013, 2013, doi: 10.1155/2013/385940.
[17] A. Dorgalaleh et al., “Effect of Thyroid Dysfunctions on Blood Cell Count and Red Blood Cell Indice,” Iran. J. Pediatr. Hematol. Oncol., vol. 3, no. 2, p. 73, 2013.
[18] X. Chen et al., “Relationship of gender and age on thyroid hormone parameters in a large Chinese population,” Arch. Endocrinol. Metab., vol. 64, pp. 52–58, 2019, doi: 10.20945/2359-3997000000179.
[19] P. N. Taylor et al., “Global epidemiology of hyperthyroidism and hypothyroidism,” Nat. Rev. Endocrinol., vol. 14, no. 5, pp. 301–316, 2018, doi: 10.1038/nrendo.2018.18.
[20] L. Bartalena, F. Bogazzi, M. L. Tanda, L. Manetti, E. Dell’Unto, and E. Martino, “Cigarette smoking and the thyroid,” Eur. J. Endocrinol., vol. 133, no. 5, pp. 507–512, 1995, doi: 10.1530/eje.0.1330507.
[21] K. Mann, “Risk of smoking in thyroid-associated orbitopathy.,” Exp. Clin. Endocrinol. Diabetes, vol. 107, no. S 05, pp. S164–S167, 1999, doi: 10.1055/s-0029-1212176.
[22] L. Hegedüs, T. H. Brix, and P. Vestergaard, “Relationship between cigarette smoking and Graves’ ophthalmopathy,” J. Endocrinol. Invest., vol. 27, pp. 256–271, 2004, doi: 10.1007/bf03345276.
[23] D. Kapoor and T. H. Jones, “Smoking and hormones in health and endocrine disorders,” Eur. J. Endocrinol., vol. 152, no. 4, pp. 491–499, 2005, doi: 10.1530/eje.1.01867.
[24] N.K. Kayumova, J.A. Nazarova, L.Kh. Mamadinova, I.A. Abbosova, & G.T. Abduvalieva. (2023). Assessment Of Quality Of Life And Cognitive Function In Patients With Primary Hypothyroidism. Journal of Population Therapeutics and Clinical Pharmacology, 30(14), 249–255. https://doi.org/10.47750/jptcp.2023.30.14.033
[25] T. Senturk, L. D. Kozaci, F. Kok, G. Kadikoylu, and Z. Bolaman, “Proinflammatory cytokine levels in hyperthyroidism,” Clin. Investig. Med., vol. 26, no. 2, pp. 58–63, 2003.
[26] Y. H. Juma’a and R. H. Allami, “The Association of TSHR Gene rs2268458 Polymorphism with Thyroid Disorders (Hyperthyroidism and Hypothyroidism) in a Sample of Iraqi Patients,” J. Forensic Med., vol. 15, no. 3, 2021, doi: 10.37506/ijfmt.v15i3.15509.
[27] X. Zhu and S. Y. Cheng, “New insights into regulation of lipid metabolism by thyroid hormone,” Curr. Opin. Endocrinol. Diabetes Obes., vol. 17, no. 5, pp. 408–413, 2010, doi: 10.1097/MED.0b013e32833d6d46.
[28] A. Ferdian, BSP. Pratondo, AP. Arifin, TR. Intansari, Y. Choiri, VC. Tansuri, A. Zahra, R. Ilmansyah, IGYP. Ananda and W. Pratiwi (2023) “Characteristics Of Patients with Grave’s Disease with ECG Sick Node Dysfunction (SND) With History of Thyroidectomy and PTU Treatment”, Journal of Population Therapeutics and Clinical Pharmacology, 30(13), pp. 80–97. doi: 10.47750/jptcp.2023.30.13.008.
[29] H. Nishitani, K. Okamura, S. Noguchi, K. Inoue, Y. Morotomi, and M. Fujishima, “Serum lipid levels in thyroid dysfunction with special reference to transient elevation during treatment in hyperthyroid graves’ disease,” Horm. Metab. Res., vol. 22, no. 9, pp. 490–493, 1990, doi: 10.1055/s-2007-1004953.
[30] A. W. C. Kung, R. W. C. Pang, I. Lauder, K. S. L. Lam, and E. D. Janus, “Changes in serum lipoprotein(a) and lipids during treatment of hyperthyroidism,” Clin. Chem., vol. 41, no. 2, pp. 226–231, 1995, doi: 10.1093/clinchem/41.2.226.
[31] D. G. Yavuz, M. Yüksel, O. Deyneli, Y. Ozen, H. Aydin, and S. Akalin, “Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goiter patients,” Clin. Endocrinol. (Oxf)., vol. 61, no. 4, pp. 515–521, 2004, doi: 10.1111/j.1365-2265.2004.02123.x.
[32] M. Peppa, G. Betsi, and G. Dimitriadis, “Lipid Abnormalities and Cardiometabolic Risk in Patients with Overt and Subclinical Thyroid Disease,” J. Lipids, vol. 2011, pp. 1–9, 2011, doi: 10.1155/2011/575840.
[33] M. Kammoun-Krichen et al., “Association analysis of interleukin-1 gene polymorphisms in autoimmune thyroid diseases in the Tunisian population,” Eur. Cytokine Netw., vol. 18, no. 4, pp. 17–21, 2007, doi: 10.1684/ecn.2007.0104.
[34] K. Lacka et al., “Interleukin-1beta gene (IL-1beta) polymorphisms (SNP -511 and SNP +3953) in thyroid-associated ophthalmopathy (TAO) among the Polish population.,” Curr. Eye Res., vol. 34, no. 3, pp. 215–220, Mar. 2009, doi: 10.1080/02713680802699390.
[35] O. Khalilzadeh et al., “Graves’ ophthalmopathy and gene polymorphisms in interleukin-1α, interleukin-1β, interleukin-1 receptor and interleukin-1 receptor antagonist,” Clin. Exp. Ophthalmol., vol. 37, no. 6, pp. 614–619, 2009, doi: 10.1111/j.1442-9071.2009.02093.x.
[36] M. L. Chen, N. Liao, H. Zhao, J. Huang, and Z. F. Xie, “Association between the IL1B (-511), IL1B (+3954), IL1RN (VNTR) polymorphisms and Graves’ disease risk: A meta-analysis of 11 case-control studies,” PLoS One, vol. 9, no. 1, p. e86077, 2014, doi: 10.1371/journal.pone.0086077.
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Nov 16, 2023
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Talal Murshed Odah al Jaraah, Gholamreza Dehghan, & Leila Sadeghi. (2023). ASSOCIATION BETWEEN PROINFLAMMATORY INTERLEUKIN-1 ß (IL1B) POLYMORPHISM AND HYPERTHYROIDISM IN IRAQI PATIENTS. Journal of Population Therapeutics and Clinical Pharmacology, 30(18), 2992-3001. https://doi.org/10.53555/jptcp.v30i18.3364
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Author Biographies
Talal Murshed Odah al Jaraah
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Gholamreza Dehghan
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Leila Sadeghi
Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
How to Cite
Talal Murshed Odah al Jaraah, Gholamreza Dehghan, & Leila Sadeghi. (2023). ASSOCIATION BETWEEN PROINFLAMMATORY INTERLEUKIN-1 ß (IL1B) POLYMORPHISM AND HYPERTHYROIDISM IN IRAQI PATIENTS. Journal of Population Therapeutics and Clinical Pharmacology, 30(18), 2992-3001. https://doi.org/10.53555/jptcp.v30i18.3364