Genetic Variants of Bank1 Gene in Autoimmune Thyroid Diseases: A Case-Control Association Study

Abstract

Objective:

To investigate BANK1 gene variation, and its association with autoimmune thyroid disease and clinical features.

Method:

We genotyped 3 single nucleotide polymorphisms (SNPs) rs10516487, rs3733197 and rs4522865 of BANK1 gene in 667 patients with autoimmune thyroid diseases (417 with Graves’ disease and 250 with Hashimoto’s thyroiditis) and 301 healthy controls. The Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform was used to detect the 3 SNPs.

Results:

There was a significant association in rs3733197 A allele and AITD patients (P=0.043). SNP rs3733197 A allele was found in 29.63% chromosome of AITD patients who are 18 years old or below, compared with 19.90% chromosome in those 19 years or above (P=0.017). Also SNP rs3733197 A allele showed a significant association in HT patients when compared with controls (P=0.031, OR=0.73 and 95% CI=0.55–0.97). Stratification for specific autoantibodies in AITD patients TGAb positive when compared with SE (shared epitope) positive showed a significant association in rs3733197 SNP (P=0.010, OR=0.68 and 95%=CI 0.51–0.91). However, no significant association was found between 3 SNPs and GD.

Conclusion:

Our findings suggest the existence of association between BANK1 gene and AITD thus adding BANK1 gene to the list of the predisposing genes to AITD.

Key words

BANK1 - single nucleotide ­polymorphisms (SNPs) - autoimmune thyroid disease - Graves’ disease - Hashimoto’s thyroiditis

• References

• 1 Tomer Y, Huber A. The etiology of autoimmune thyroid disease: a story of genes and environment. J Autoimmun 2009; 32: 231-239
• 2 Lavard L, Madsen HO, Perrild H et al. HLA- class 2 association in juvenile GD;indication of a strong protective role of DRB1*0701,DQA1*0201. Tissue Antigens 1997; 50: 639-641
• 3 Gu LQ, Zhu W, Zhao SX et al. Clinical associations of the genetic variants of CTLA-4, Tg, TSHR, PTPN22, PTPN12 and FCRL3 in patients with Graves’ disease. Clin Endocinol (Oxf) 2010; 72: 248-255
• 4 Velaga MR, Wilson V, Jennnings CE et al. The codon 620 tryptphan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves’ disease. J Clin Endocrinol Metab 2004; 89: 5862-5865
• 5 Hiratatani H, Bowden DW, Ikegami S et al. Multiple SNPs in intron 7 of thyroitropin receptor are associated with Graves’ disease. J Clin Endocrinol Metab 2005; 90: 2898-2903
• 6 Simmonds MJ, Gough SC. Unravelling the genetic complexity of autoimmune thyroid disease: HLA,CTLA-4 and beyond. Clin Exp Immunol 2004; 136: 1-10
• 7 Bednarezuk T, Hiromatsu Y, Fukutani T et al. Association of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)gene polymorphism and non genetic factors with Graves’ ophthalmopathy in European and Japanese populations. Eur J Endocrinol 2003; 148: 13-18
• 8 Zhang X, Fei Z, Wan J et al. Association analysis of BANK1 gene with psoriasis in Southern Han Chinese. Int J Immunogenet 2011; 38: 507-512
• 9 Yokoyama K, SuIh IH, Tezuka T et al. BANK1 regulates BCR- induced calcium mobilization by promoting tyrosine phosphorylation of IP(3) receptor. EMBO J 2002; 21: 83-92
• 10 Kozyrev SV, Abelson AK, Wojcik J et al. Functional in B cell variants BANK1 are associated with systemic lupus erythematosus. Nat Genet 2008; 40: 484
• 11 Chang YK, Yang W, Zhao M et al. Association of BANK1 and TNSF4 with systemic lupus erythematosus in Hong Kong Chinese. Genes Immun 2009; 10: 414-420
• 12 Dieudé P, Wipff J, Guedj M et al. BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects IRF5 and STAT4. Arthritis Rheum 2009; 60: 3447-3454
• 13 Rueda B, Gourgh P, Broen J et al. BANK1 functional variants are associated with susceptibility to diffuse systemic sclerosis in Caucasians. Ann Rheum Dis 2010; 69: 700-705
• 14 Kurosaki T. Regulation of B-cell signal transduction by adaptor proteins. Nat Rev Immunol 2002; 2: 354-363
• 15 Guo L, Deshmukh H, Lu R et al. Replication of the BANK1 genetic association with systemic lupus erythmatosus in European-derived population. Genes Immun 2009; 10: 531-538
• 16 Martin F, Chan AC. B cell immunology in disease:evolving concepts from the clinic. Annu Rev Immunol 2006; 24: 467-496
• 17 Orozoco G, Abelson AK, Gonzálenz-Gay MA et al. Study of functional variants of the BANK1 gene in rheumatoid arthritis. Arthritis Rheum 2009; 60: 372-379
• 18 Guan M, Yu B, Wan J et al. Identification of BANK1 polymorphisms by unlabelled probe high resolution melting: association with systemic lupus erythematosus susceptibility and autoantibody production production in Han Chinese. Rheumatology(Oxf) 2011; 50: 473-480
• 19 Dunn JT, Dunn AD. Update on the intrathyroidal iodine metabolism. Thyroid 2001; 11: 407-414
• 20 Feldt-Rasmussen U, Hoier-Masden M, Bech K et al. Anti- thyroidal peroxidase antibodies in thyroid disorders and non thyroid auto-immune diseases. Autoimmunity 1991; 9: 245-254
• 21 Wielbolt J, Achterbergh R, Den Boer A et al. Clustering of additional autoimmunity behaves differently in Hashimoto’s patients compared with Graves’ patients. Eur J Endocrinol 2011; 164: 789-794