Protein Tyrosine Phosphatase Non-receptor 22 Gene C1858T Polymorphism in Patients with Coexistent Type 2 Diabetes and Hashimoto’s Thyroiditis

Year 2014, , 37 - 42, 07.08.2014

Funda Bulut Deniz Erol Halit Elyas Halil Doğan Fethi Ahmet Özdemir Lezan Keskin

https://doi.org/10.5152/balkanmedj.2014.9418

Abstract

Background: A protein tyrosine phosphatase non-receptor type 22 (PTPN22) C1858T gene polymorphism has been reported to be associated with both Type 2 diabetes mellitus (T2DM) and Hashimoto's thyroiditis (HT) separately. However, no study has been conducted to explore the C1858T polymorphism in T2DM and HT coexistent cases up to now. Aims: The study aimed to determine whether a relationship exists or not between the PTPN22 C1858T polymorphism and this coexistent patient group. Study Design: Case-control study. Methods: Peripheral blood samples from 135 T2DM patients, 102 patients with coexistent T2DM+HT, 71 HT patients and 135 healthy controls were collected into ethylenediaminetetraacetic acid (EDTA) anticoagulant tubes and genomic DNA was extracted. The PTPN22 C1858T polymorphism was analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. Results: Statistically significant differences were not observed between the patient and control groups. This study demonstrated a statistically significant association between both the CT genotype and the T allele in the female patient group with coexistent T2DM+HT (CT genotype: p=0.04; T allele: p=0.045) with a statistically significant association between the CT genotype and the mean values of body mass index (BMI) and free T3 levels (FT3) (BMI: p=0.044 and FT3: p=0.021) that was detected in the patient group with coexistent T2DM+HT. The minor genotype TT was observed in none of the groups in this study. The CT genotype frequency was [number (frequency): 5 (3.8%), 7 (6.86%), 5 (7.04%), 3 (2.22%), while the T allele frequency was 5 (1.86%), 7 (3.44%), 5 (3.53%) and 3 (1.12%)] in the T2DM, T2DM+HT, HT and control groups, respectively. Conclusion: Our data suggest that the PTPN22 1858T allele and the CT genotype are associated with increased risk in female patients for coexistent T2DM+HT. The CT genotype was associated with high mean BMI and free T3 values in the patient group with coexistent T2DM+HT. These results demonstrate that T allele carriers were more often in the T2DM+HT group than in the T2DM group. Therefore, the combination of T2DM and HT with female gender may have higher T allele carriage in comparison to the T2DM only and male groups.

Keywords

Hashimoto’s thyroiditis, polymorphism, protein tyrosine phosphatase non-receptor type 22, type 2 diabetes

Protein Tyrosine Phosphatase Non-receptor 22 Gene C1858T Polymorphism in Patients with Coexistent Type 2 Diabetes and Hashimoto’s Thyroiditis

Abstract

References

• Vondra K, Vrbikova J, Dvorakova K. Thyroid gland diseases in adult patients with diabetes mellitus. Minerva Endocrinol 2005;30:217-36.
• Schroner Z, Lazurova I, Petrovicova J. Autoimmune thyroid diseases in patients with diabetes mellitus. Bratisl Lek Listy 2008;109:125-9.
• Bindra A, Braunstein GD. Thyroiditis. Am Fam Physician 2006;15:1769-76.
• Michels AW, Eisenbarth GS. Immunologic endocrine disorders. J Allergy Clin Immunol 2010;125:226-37. [CrossRef]
• Fink H, Hintze G. Autoimmune thyroiditis (Hashimoto’s thyroiditis): current diagnostics and therapy. Med Klin (Munich) 2010;105:485-93. [CrossRef]
• Radaideh AR, Nusier MK, Amari FL, Bateiha AE, El-Khateeb MS, Naser AS, et al. Thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan. Saudi Med J 2004;25:1046-50.
• Kadiyala R, Peter R, Okosieme OE.Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies. Int J Clin Pract 2010;64:1130-9. [CrossRef]
• Rampersaud E, Damcott CM, Fu M, Shen H, McArdle P, Shi X, et al. Identification of novel candidate genes for type 2 diabetes from a genome-wide association scan in the Old Order Amish: evidence for replication from diabetes-related quantitative traits and from independent populations. Diabetes 2007;56:3053-62. [CrossRef]
• Cantrell RA, Alatorre CI, Davis EJ, Zarotsky V, Le Nestour E, Carter GC, et al. A review of treatment response in type 2 diabetes: assessing the role of patient heterogeneity. Diabetes Obes Metab 2010;12:845-57. [CrossRef]
• Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87:4-14. [CrossRef]
• Jin W, Patti ME. Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes. Clin Sci 2009;116:99-111. [CrossRef]
• Jacobson EM, Tomer Y. The CD40, CTLA-4, Thyroglobulın, TSH receptor, and PTPN22 gene quıntet and ıts contrıbutıon to thyroıd autoımmunıty: back to the future. J Autoimmun 2007;28:85-98. [CrossRef]
• Levin L, Tomer Y. The etiology of autoimmune diabetes and thyroiditis: evidence for common genetic susceptibility. Autoimmun Rev 2003;2:377-86. [CrossRef]
• Ridderstråle M, Groop L. Genetic dissection of type 2 diabetes. Mol Cell Endocrinol 2009;297:10-7. [CrossRef]
• Andersen MK, Lundgren V, Turunen JA, Forsblom C, Isomaa B, Groop PH, et al. Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years. Diabetes Care 2010;33:2062-4. [CrossRef]
• Cervin C, Lyssenko V, Bakhtadze E, Lindholm E, Nilsson P, Tuomi T, et al. Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes and type 2 diabetes. Diabetes 2008;57:1433-7. [CrossRef]
• Douroudis K, Prans E, Haller K, Nemvalts V, Rajasalu T, Tillmann V, et al. Protein tyrosine phosphatase non-receptor type 22 gene variants at position 1858 are associated with type 1 and type 2 diabetes in Estonian population. Tissue Antigens 2008;72:425-30. [CrossRef]
• Hu C, Zhang R, Wang C, Wang J, Ma X, Lu J, et al. PARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population. PLoS One 2009;28;4:e7643.
• Prokopenko I, McCarthy MI, Lindgren CM. Type 2 diabetes: new genes, new understanding. Trends Genet 2008;24:613-21. [CrossRef]
• Tomer Y, Huber A. The etiology of autoimmune thyroid disease: a story of genes and environment. J Autoimmun 2009;32:231-9. [CrossRef]
• Kawasaki E, Awata T, Ikegami H, Kobayashi T, Maruyama T, Nakanishi K, et al. Systematic Search for Single Nucleotide Polymorphisms in a Lymphoid Tyrosine Phosphatase Gene (PTPN22): Association Between a Promoter Polymorphism and Type 1 Diabetes in Asian Populations. Am J Med Genet A 2006;15;140:586-93. [CrossRef]
• Zhang ZH, Chen F, Zhang XL, Jin Y, Bai J, Fu SB. PTPN22 allele polymorphisms in 15 Chinese populations. Int J Immunogenet 2008;35:433-7. [CrossRef] Tfayli H, Arslanian S. Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon. Arq Bras Endocrinol Metabol 2009;53:165-74. [CrossRef]
• Zeyda M, Stulnig TM. Obesity, inflammation, and insulin resistance—a mini-review. Gerontology 2009;55:379-86. [CrossRef]
• Usui I, Tobe K. The role of inflammation in the development of insulin resistance in type 2 diabetes. Nippon Rinsho 2011;69:555-62.
• Brooks-Worrell B, Palmer JP. Immunology in the Clinic Review Series; focus on metabolic diseases: development of islet autoimmune disease in type 2 diabetes patients: potential sequelae of chronic inflammation. Clin Exp Immunol 2012;167:40-6. [CrossRef]
• Vang T, Miletic AV, Bottini N, Mustelin T. Protein tyrosine phosphatase PTPN22 in human autoimmunity. Autoimmunity 2007;40:453-61. [CrossRef] Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK, et al. The PTPN22 C1858T functional polymorphism and autoimmune diseases—a metaanalysis. Rheumatology 2007;46:49-56. [CrossRef]
• Tomer Y, Menconi F. Type 1 diabetes and autoimmune thyroiditis: the genetic connection. Thyroid 2009;19:99-102. [CrossRef]
• Dultz G, Matheis N, Dittmar M, Röhrig B, Bender K, Kahaly GJ. The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes. Thyroid 2009;19:143. [CrossRef]
• Lee YH, Song GG. Meta-analysis of the family-based association between the PTPN22 C1858T polymorphism and type 1 diabetes. Mol Biol Rep 2013;40:211-5. [CrossRef]
• Criswell LA, Pfeiffer KA, Lum RF, Gonzales B, Novitzke J, Kern M, et al. Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620 W allele associates with multiple autoimmune phenotypes. Am J Hum Genet 2005;76:561-71. [CrossRef]
• Luo L, Cai B, Liu F, Hu X, Wang L. Association of Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) C1858T gene polymorphism with susceptibility to autoimmune thyroid diseases: a meta-analysis. Endocr J 2012;59:439-45. [CrossRef]