Abstract
Purpose
p53, which is encoded by the tumor suppressor gene TP53, plays a crucial role in the regulation of mechanisms of cell cycle arrest and apoptosis. Some SNPs of TP53, involving a different apoptotic ability of p53, have been associated with increased susceptibility to develop autoimmune diseases as well as cancer. We investigated the genotypic distribution of TP53 exon 4 SNPs in a cohort of Caucasian patients affected by Hashimoto’s thyroiditis (HT).
Methods
Peripheral blood for DNA extraction was collected from 109 Caucasian unrelated subjects, 79 HT patients and 30 healthy controls. SNPs analysis was carried out by amplification and sequencing of exon 4 TP53.
Results
For the Pro72Arg (rs 1042522) SNP we found these rates in HT patients: 11.4 % wild-type C/C (Pro72Pro), 24.0 % heterozygous G/C (Pro72Arg), 64.6 % homozygous G/G (Arg72Arg). The corresponding rates in healthy controls were 10, 46.7 and 43.3 %, respectively. Thus, significantly different were G/C heterozygosity (24.0 vs 46.7 %, p = 0.039) and G/G homozygosity (64.6 vs 43.3 %, p = 0.042). These differences were also confirmed when comparing our study population to published Caucasian control groups. The other described SNPs (Pro34Pro rs 11575998, Pro36Pro rs1800370, Pro47Ser rs1800371, and Arg110Leu rs 11540654) were absent or very rare in our study population.
Conclusions
Our preliminary data, the first on a Caucasian population, indicate an increased prevalence of the homozygous genotype Arg/Arg and a decreased prevalence of heterozygous genotype Arg/Pro of rs 1042522 in HT patients compared to controls, suggesting that such SNP may contribute to confer susceptibility to HT.
Similar content being viewed by others
References
Vousden KH, Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8:275–283
Hainaut P, Hernandez T, Robinson A (1998) IARC Database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualization tools. Nucleic Acids Res 21:205–213
Belyi VA, Ak P, Markert E (2010) The origins and evolution of the p53 family of genes. Cold Spring Harb Perspect Biol 6:a001198
Whibley C, Pharoah PD, Hollstein M (2009) p53 polymorphisms: cancer implications. Nat Rev Cancer 9:95–107
Krammer PH (2000) CD 95’s deadly mission in the immune system. Nature 407:789–795
Zhang S, Zheng M, Kibe R (2011) Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis. FASEB J 25:2387–2398
Kawashima H, Takatori H, Suzuki K (2013) Tumor suppressor p53 inhibits systemic autoimmune diseases by inducing regulatory T cells. J Immunol 191:3614–32623
Orsted DD, Bojesen SE, Tybjaerg-Hansen A (2007) Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population. J Exp Med 204:1295–1301
Puente XS, Velasco G, Gutiérrez-Fernández A (2006) Comparative analysis of cancer genes in the human and chimpanzee genomes. BMC Genom 7:15
Sjalander A, Birgander R, Saha N (1996) p53 polymorphisms and haplotypes show distinct differences between major ethnic groups. Hum Hered 46:41–48
Dumont P, Leu JI, Della Pietra AC (2003) The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 33:357–365
Boltze C, Roessner O, Landt E (2002) Homozygous proline at codon 72 of p53 as a potential risk factor favoring the development of undifferentiated thyroid carcinoma. Int J Oncol 21:1151–1154
Granja F, Morari J, Morari EC (2004) Proline homozygosity in codon 72 of p53 is a factor of susceptibility for thyroid cancer. Cancer Lett 210:151–157
Wang F, Wang P, Wang B (2014) Association between TP53 Arg72Pro polymorphism and thyroid carcinoma risk. Tumour Biol 35:2723–2728
Felley-Bosco E, Weston A, Cawley HM (1993) Functional studies of a germ-line polymorphism at codon 47 within the p53 gene. Am J Hum Genet 53:752–759
Li X, Dumont P, Della Pietra A (2005) The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 280:24245–24251
Franchi A, Sardi I, Cetica V (2009) Pediatric sinonasal neuroendocrine carcinoma after treatment of retinoblastoma. Hum Pathol 40:750–755
Pearce EN, Farwell AP, Braverman LE (2003) Thyroiditis. N Eng J Med 348:2646–2655
Aghini-Lombardi F, Vitti P, Antonangeli L, Southern Italy Study Group for Iodine Deficiency Disorders (2013) The size of the community rather than its geographical location better defines the risk of iodine deficiency: results of an extensive survey in Southern Italy. J Endocrinol Invest 36:282–286
Kleimbaum DG, Klein M (2002) A self-learning text. Logistic regression, Springer, New York, pp 7–26
Weetman AP (2012) The immunopathogenesis of chronic autoimmune thyroiditis one century after hashimoto. Eur J Endocrinol 1:243–250
Weetman AP (2009) The genetics of autoimmune thyroid disease. Horm Metabol Res 41:421–425
Prummel MF, Strieder T, Wiersinga WM (2004) The environment and autoimmune thyroid diseases. Eur J Endocrinol 150:605–618
Guerra A, Sapio MR, Carrano M, Di Stasi V, Volpe A, Murino A, Izzo G, Vitale M (2013) Prevalence of Dio 2(T92A) polymorphism and its association with thyroid autoimmunity. J Endocrinol Invest 36:303–306
Agretti P, De Marco G, Di Cosmo C, Bagattini B, Ferrarini E, Montanelli L, Vitti P, Tonacchera M (2014) Frequency and effect on serum TSH of phosphodiesterase 8B (PDE8B) gene polymorphisms in patients with sporadic nonautoimmune subclinical hypothyroidism. J Endocrinol Invest 37:189–194
Yamanishi Y, Boyle DL, Pinkoski MJ (2002) Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol 160:123–130
Zheng SJ, Lamhamedi-Cherradi SE, Wang P (2005) Tumor suppressor p53 inhibits autoimmune inflammation and macrophage function. Diabetes 54:1423–1428
Okuda M, Bernard CC (2003) Regulatory role of p53 in experimental autoimmune encephalomyelitis. J Neuroimmunol 135:29–37
Yao Q, Wang S, Glorioso JC (2001) Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. Mol Ther 3:901–910
Yamanishi Y, Boyle DL, Green DR (2005) p53 tumor suppressor gene mutations in fibroblast-like synoviocytes from erosion synovium and non-erosion synovium in rheumatoid arthritis. Arthritis Res Ther 7:R12–R18
Lee YH, Bae SC, Choi SJ (2012) Associations between the p53 codon 72 polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis. Lupus 21:430–437
Hussain SP, Amstad P, Raja K (2000) Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res 60:3333–3337
Manca Bitti ML, Saccucci P, Bottini E (2010) p53 codon 72 polymorphism and type 1 diabetes mellitus. J Pediat Endocrinol Metab 23:291–292
Bufalo NE, Santos RB, Cury AN (2008) Genetic polymorphisms associated with cigarette smoking and the risk of Graves’ disease. Clin Endocrinol (Oxf) 6:982–987
Chen RH, Chang CT, Wang TY (2008) p53 codon 72 proline/arginine polymorphism and autoimmune thyroid diseases. J Clin Lab Anal 22:321–326
Salmaso C, Bagnasco M, Pesce G (2002) Regulation of apoptosis in endocrine autoimmunity: insights from Hashimoto’s thyroiditis and Graves’ disease. Ann N Y Acad Sci 966:496–501
Trimarchi F (2014) Clinical Endocrinology in the near future: a post-modern challenge. J Endocrinol Invest. doi:10.1007/s40618-014-0181-7
Acknowledgements
This work was not supported by any grant.
Conflict of interest
There is no potential conflict of interest and the authors have nothing to disclose.
Ethical approval
The study was approved by the local ethics committee.
Informed consent
The informed consent was obtained from the patients for publication.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ruggeri, R.M., Vicchio, T.M., Giovinazzo, S. et al. TP53 polymorphism may contribute to genetic susceptibility to develop Hashimoto’s thyroiditis. J Endocrinol Invest 38, 1175–1182 (2015). https://doi.org/10.1007/s40618-015-0292-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-015-0292-9