Skip to main content

Advertisement

SpringerLink
Log in

Association of established hypothyroidism-associated genetic variants with Hashimoto’s thyroiditis

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

Hashimoto’s thyroiditis (HT) as a chronic autoimmune disease of the thyroid gland is the most common cause of hypothyroidism. Since HT and hypothyroidism are closely related, the main aim of this study was to explore the association of established hypothyroidism single-nucleotide polymorphisms (SNPs) with HT.

Methods

The case–control dataset included 200 HT cases and 304 controls. Diagnosis of HT cases was based on clinical examination, measurement of thyroid antibodies (TgAb, TPOAb), hormones (TSH and FT4) and ultrasound examination. We genotyped and analysed 11 known hypothyroidism-associated genetic variants. Case–control association analysis was performed in order to test each SNP for the association with HT using logistic regression model. Additionally, each SNP was tested for the association with thyroid-related quantitative traits (TPOAb levels, TgAb levels and thyroid volume) in HT cases only using linear regression.

Results

We identified two genetic variants nominally associated with HT rs3184504 in SH2B3 gene (P = 0.0135, OR = 0.74, 95% CI = 0.57–0.95) and rs4704397 in PDE8B gene (P = 0.0383, OR = 1.32, 95% CI = 1.01–1.74). The SH2B3 genetic variant also showed nominal association with TPOAb levels (P = 0.0163, β = −0.46) and rs4979402 inside DFNB31 gene was nominally associated with TgAb levels (P = 0.0443, β = 0.41).

Conclusions

SH2B3 gene has previously been associated with susceptibility to several autoimmune diseases, whereas PDE8B has been associated with TSH levels and suggested to modulate thyroid physiology that may influence the manifestation of thyroid disease. Identified loci are novel and biologically plausible candidates for HT development and represent good basis for further exploration of HT susceptibility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Weetman AP (2013) The immunopathogenesis of chronic autoimmune thyroiditis one century after hashimoto. Eur Thyroid J 1(4):243–250. doi:10.1159/000343834

    PubMed  Google Scholar 

  2. Zaletel K, Gaberscek S (2011) Hashimoto’s thyroiditis: from genes to the disease. Curr Genom 12(8):576–588. doi:10.2174/138920211798120763

    Article  CAS  Google Scholar 

  3. Zaletel K (2007) Determinants of thyroid autoantibody production in Hashimoto’s thyroiditis. Expert Rev Clin Immunol 3(2):217–223. doi:10.1586/1744666x.3.2.217

    Article  CAS  PubMed  Google Scholar 

  4. Tam AA, Kaya C, Ucler R, Dirikoc A, Ersoy R, Cakir B (2015) Correlation of normal thyroid ultrasonography with thyroid tests. Quant Imaging Med Surg 5(4):569–574. doi:10.3978/j.issn.2223-4292.2015.08.06

    PubMed  PubMed Central  Google Scholar 

  5. Tagami T, Tamanaha T, Shimazu S, Honda K, Nanba K, Nomura H, Yoriko SU, Usui T, Shimatsu A, Naruse M (2010) Lipid profiles in the untreated patients with Hashimoto thyroiditis and the effects of thyroxine treatment on subclinical hypothyroidism with Hashimoto thyroiditis. Endocr J 57(3):253–258

    Article  CAS  PubMed  Google Scholar 

  6. Wiersinga WM (2016) Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab 31

  7. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F et al. (1995) The incidence of thyroid disorders in the community: a 20-year follow-up of the Whickham Survey. Clin Endocrinol Oxf 43(1):55–68

    Article  CAS  PubMed  Google Scholar 

  8. Jacobson DL, Gange SJ, Rose NR, Graham NM (1997) Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol 84(3):223–243

    Article  CAS  PubMed  Google Scholar 

  9. McLeod DS, Cooper DS (2012) The incidence and prevalence of thyroid autoimmunity. Endocrine 42(2):252–265. doi:10.1007/s12020-012-9703-2

    Article  CAS  PubMed  Google Scholar 

  10. Golden SH, Robinson KA, Saldanha I, Anton B, Ladenson PW (2009) Clinical review: prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review. J Clin Endocrinol Metab 94(6):1853–1878. doi:10.1210/jc.2008-2291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Simmonds MJ (2013) GWAS in autoimmune thyroid disease: redefining our understanding of pathogenesis. Nat Rev Endocrinol 9(5):277–287. doi:10.1038/nrendo.2013.56

    Article  CAS  PubMed  Google Scholar 

  12. Gough SC, Simmonds MJ (2007) The HLA region and autoimmune disease: associations and mechanisms of action. Curr Genom 8(7):453–465. doi:10.2174/138920207783591690

    Article  CAS  Google Scholar 

  13. Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, Rainbow DB, Hunter KM, Smith AN, Di Genova G, Herr MH, Dahlman I, Payne F, Smyth D, Lowe C, Twells RC, Howlett S, Healy B, Nutland S, Rance HE, Everett V, Smink LJ, Lam AC, Cordell HJ, Walker NM, Bordin C, Hulme J, Motzo C, Cucca F, Hess JF, Metzker ML, Rogers J, Gregory S, Allahabadia A, Nithiyananthan R, Tuomilehto-Wolf E, Tuomilehto J, Bingley P, Gillespie KM, Undlien DE, Ronningen KS, Guja C, Ionescu-Tirgoviste C, Savage DA, Maxwell AP, Carson DJ, Patterson CC, Franklyn JA, Clayton DG, Peterson LB, Wicker LS, Todd JA, Gough SC (2003) Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423(6939):506–511. doi:10.1038/nature01621

    Article  CAS  PubMed  Google Scholar 

  14. Velaga MR, Wilson V, Jennings CE, Owen CJ, Herington S, Donaldson PT, Ball SG, James RA, Quinton R, Perros P, Pearce SH (2004) The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves’ disease. J Clin Endocrinol Metab 89(11):5862–5865. doi:10.1210/jc.2004-1108

    Article  CAS  PubMed  Google Scholar 

  15. Oryoji D, Ueda S, Yamamoto K, Yoshimura Noh J, Okamura K, Noda M, Watanabe N, Yoshihara A, Ito K, Sasazuki T (2015) Identification of a Hashimoto thyroiditis susceptibility locus via a genome-wide comparison with Graves’ disease. J Clin Endocrinol Metab 100(2):E319–E324. doi:10.1210/jc.2014-3431

    Article  CAS  PubMed  Google Scholar 

  16. Santos LR, Duraes C, Mendes A, Prazeres H, Alvelos MI, Moreira CS, Canedo P, Esteves C, Neves C, Carvalho D, Sobrinho-Simoes M, Soares P (2014) A polymorphism in the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto’s thyroiditis susceptibility. J Clin Endocrinol Metab 99(4):E719–E723. doi:10.1210/jc.2013-3539

    Article  CAS  PubMed  Google Scholar 

  17. Denny JC, Crawford DC, Ritchie MD, Bielinski SJ, Basford MA, Bradford Y, Chai HS, Bastarache L, Zuvich R, Peissig P, Carrell D, Ramirez AH, Pathak J, Wilke RA, Rasmussen L, Wang X, Pacheco JA, Kho AN, Hayes MG, Weston N, Matsumoto M, Kopp PA, Newton KM, Jarvik GP, Li R, Manolio TA, Kullo IJ, Chute CG, Chisholm RL, Larson EB, McCarty CA, Masys DR, Roden DM, de Andrade M (2011) Variants near FOXE1 are associated with hypothyroidism and other thyroid conditions: using electronic medical records for genome- and phenome-wide studies. Am J Hum Genet 89(4):529–542. doi:10.1016/j.ajhg.2011.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Eriksson N, Tung JY, Kiefer AK, Hinds DA, Francke U, Mountain JL, Do CB (2012) Novel associations for hypothyroidism include known autoimmune risk loci. PLoS One 7(4):e34442. doi:10.1371/journal.pone.0034442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rudan I, Marusic A, Jankovic S, Rotim K, Boban M, Lauc G, Grkovic I, Dogas Z, Zemunik T, Vatavuk Z, Bencic G, Rudan D, Mulic R, Krzelj V, Terzic J, Stojanovic D, Puntaric D, Bilic E, Ropac D, Vorko-Jovic A, Znaor A, Stevanovic R, Biloglav Z, Polasek O (2009) “10001 Dalmatians:” Croatia launches its national biobank. Croat Med J 50(1):4–6

    Article  PubMed  PubMed Central  Google Scholar 

  20. Brcic L, Baric A, Gracan S, Brdar D, Torlak Lovric V, Vidan N, Zemunik T, Polasek O, Barbalic M, Punda A, Boraska Perica V (2016) Association of established thyroid peroxidase autoantibody (TPOAb) genetic variants with Hashimoto’s thyroiditis. Autoimmunity. doi:10.1080/08916934.2016.1191475

    PubMed  Google Scholar 

  21. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi:10.1086/519795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gauderman WJ (2003) Candidate gene association analysis for a quantitative trait, using parent-offspring trios. Genet Epidemiol 25(4):327–338. doi:10.1002/gepi.10262

    Article  PubMed  Google Scholar 

  23. Zhernakova A, Elbers CC, Ferwerda B, Romanos J, Trynka G, Dubois PC, de Kovel CG, Franke L, Oosting M, Barisani D, Bardella MT, Finnish Celiac Disease Study G, Joosten LA, Saavalainen P, van Heel DA, Catassi C, Netea MG, Wijmenga C (2010) Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. Am J Hum Genet 86(6):970–977. doi:10.1016/j.ajhg.2010.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Perez-Garcia A, Ambesi-Impiombato A, Hadler M, Rigo I, LeDuc CA, Kelly K, Jalas C, Paietta E, Racevskis J, Rowe JM, Tallman MS, Paganin M, Basso G, Tong W, Chung WK, Ferrando AA (2013) Genetic loss of SH2B3 in acute lymphoblastic leukemia. Blood 122(14):2425–2432. doi:10.1182/blood-2013-05-500850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Auburger G, Gispert S, Lahut S, Ömür Ö, Damrath E, Heck M, Başak N (2014) 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? World J Diabetes 5(3):316–327. doi:10.4239/wjd.v5.i3.316

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kus A, Szymanski K, Peeters RP, Miskiewicz P, Porcu E, Pistis G, Sanna S, Naitza S, Ploski R, Medici M, Bednarczuk T (2015) The association of thyroid peroxidase antibody risk loci with susceptibility to and phenotype of Graves’ disease. Clin Endocrinol Oxf 83(4):556–562. doi:10.1111/cen.12640

    Article  CAS  PubMed  Google Scholar 

  27. Plagnol V, Howson JM, Smyth DJ, Walker N, Hafler JP, Wallace C, Stevens H, Jackson L, Simmonds MJ, Type 1 Diabetes Genetics C, Bingley PJ, Gough SC, Todd JA (2011) Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet 7(8):e1002216. doi:10.1371/journal.pgen.1002216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Medici M, Porcu E, Pistis G, Teumer A, Brown SJ, Jensen RA, Rawal R, Roef GL, Plantinga TS, Vermeulen SH, Lahti J, Simmonds MJ, Husemoen LL, Freathy RM, Shields BM, Pietzner D, Nagy R, Broer L, Chaker L, Korevaar TI, Plia MG, Sala C, Volker U, Richards JB, Sweep FC, Gieger C, Corre T, Kajantie E, Thuesen B, Taes YE, Visser WE, Hattersley AT, Kratzsch J, Hamilton A, Li W, Homuth G, Lobina M, Mariotti S, Soranzo N, Cocca M, Nauck M, Spielhagen C, Ross A, Arnold A, van de Bunt M, Liyanarachchi S, Heier M, Grabe HJ, Masciullo C, Galesloot TE, Lim EM, Reischl E, Leedman PJ, Lai S, Delitala A, Bremner AP, Philips DI, Beilby JP, Mulas A, Vocale M, Abecasis G, Forsen T, James A, Widen E, Hui J, Prokisch H, Rietzschel EE, Palotie A, Feddema P, Fletcher SJ, Schramm K, Rotter JI, Kluttig A, Radke D, Traglia M, Surdulescu GL, He H, Franklyn JA, Tiller D, Vaidya B, de Meyer T, Jorgensen T, Eriksson JG, O’Leary PC, Wichmann E, Hermus AR, Psaty BM, Ittermann T, Hofman A, Bosi E, Schlessinger D, Wallaschofski H, Pirastu N, Aulchenko YS, de la Chapelle A, Netea-Maier RT, Gough SC, Meyer Zu Schwabedissen H, Frayling TM, Kaufman JM, Linneberg A, Raikkonen K, Smit JW, Kiemeney LA, Rivadeneira F, Uitterlinden AG, Walsh JP, Meisinger C, den Heijer M, Visser TJ, Spector TD, Wilson SG, Volzke H, Cappola A, Toniolo D, Sanna S, Naitza S, Peeters RP (2014) Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease. PLoS Genet 10(2):e1004123. doi:10.1371/journal.pgen.1004123

    Article  PubMed  PubMed Central  Google Scholar 

  29. Strieder TG, Prummel MF, Tijssen JG, Endert E, Wiersinga WM (2003) Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clin Endocrinol Oxf 59(3):396–401

    Article  PubMed  Google Scholar 

  30. Hayashi M, Matsushima K, Ohashi H, Tsunoda H, Murase S, Kawarada Y, Tanaka T (1998) Molecular cloning and characterization of human PDE8B, a novel thyroid-specific isozyme of 3′,5′-cyclic nucleotide phosphodiesterase. Biochem Biophys Res Commun 250(3):751–756. doi:10.1006/bbrc.1998.9379

    Article  CAS  PubMed  Google Scholar 

  31. Arnaud-Lopez L, Usala G, Ceresini G, Mitchell BD, Pilia MG, Piras MG, Sestu N, Maschio A, Busonero F, Albai G, Dei M, Lai S, Mulas A, Crisponi L, Tanaka T, Bandinelli S, Guralnik JM, Loi A, Balaci L, Sole G, Prinzis A, Mariotti S, Shuldiner AR, Cao A, Schlessinger D, Uda M, Abecasis GR, Nagaraja R, Sanna S, Naitza S (2008) Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function. Am J Hum Genet 82(6):1270–1280. doi:10.1016/j.ajhg.2008.04.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rawal R, Teumer A, Volzke H, Wallaschofski H, Ittermann T, Asvold BO, Bjoro T, Greiser KH, Tiller D, Werdan K, Meyer zu Schwabedissen HE, Doering A, Illig T, Gieger C, Meisinger C, Homuth G (2012) Meta-analysis of two genome-wide association studies identifies four genetic loci associated with thyroid function. Hum Mol Genet 21(14):3275–3282. doi:10.1093/hmg/dds136

    Article  CAS  PubMed  Google Scholar 

  33. Malinowski JR, Denny JC, Bielinski SJ, Basford MA, Bradford Y, Peissig PL, Carrell D, Crosslin DR, Pathak J, Rasmussen L, Pacheco J, Kho A, Newton KM, Li R, Kullo IJ, Chute CG, Chisholm RL, Jarvik GP, Larson EB, McCarty CA, Masys DR, Roden DM, de Andrade M, Ritchie MD, Crawford DC (2014) Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE network. PLoS One 9(12):e111301. doi:10.1371/journal.pone.0111301

    Article  PubMed  PubMed Central  Google Scholar 

  34. Porcu E, Medici M, Pistis G, Volpato CB, Wilson SG, Cappola AR, Bos SD, Deelen J, den Heijer M, Freathy RM, Lahti J, Liu C, Lopez LM, Nolte IM, O’Connell JR, Tanaka T, Trompet S, Arnold A, Bandinelli S, Beekman M, Bohringer S, Brown SJ, Buckley BM, Camaschella C, de Craen AJ, Davies G, de Visser MC, Ford I, Forsen T, Frayling TM, Fugazzola L, Gogele M, Hattersley AT, Hermus AR, Hofman A, Houwing-Duistermaat JJ, Jensen RA, Kajantie E, Kloppenburg M, Lim EM, Masciullo C, Mariotti S, Minelli C, Mitchell BD, Nagaraja R, Netea-Maier RT, Palotie A, Persani L, Piras MG, Psaty BM, Raikkonen K, Richards JB, Rivadeneira F, Sala C, Sabra MM, Sattar N, Shields BM, Soranzo N, Starr JM, Stott DJ, Sweep FC, Usala G, van der Klauw MM, van Heemst D, van Mullem A, Vermeulen SH, Visser WE, Walsh JP, Westendorp RG, Widen E, Zhai G, Cucca F, Deary IJ, Eriksson JG, Ferrucci L, Fox CS, Jukema JW, Kiemeney LA, Pramstaller PP, Schlessinger D, Shuldiner AR, Slagboom EP, Uitterlinden AG, Vaidya B, Visser TJ, Wolffenbuttel BH, Meulenbelt I, Rotter JI, Spector TD, Hicks AA, Toniolo D, Sanna S, Peeters RP, Naitza S (2013) A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. PLoS Genet 9(2):e1003266. doi:10.1371/journal.pgen.1003266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Stein JL, Hibar DP, Madsen SK, Khamis M, McMahon KL, de Zubicaray GI, Hansell NK, Montgomery GW, Martin NG, Wright MJ, Saykin AJ, Jack CR Jr, Weiner MW, Toga AW, Thompson PM, Alzheimer’ s Disease Neuroimaging Initiative I (2011) Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N = 1198) using genome-wide search. Mol Psychiatry 16(9):927–937. doi:10.1038/mp.2011.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Appenzeller S, Schirmacher A, Halfter H, Baumer S, Pendziwiat M, Timmerman V, De Jonghe P, Fekete K, Stogbauer F, Ludemann P, Hund M, Quabius ES, Ringelstein EB, Kuhlenbaumer G (2010) Autosomal-dominant striatal degeneration is caused by a mutation in the phosphodiesterase 8B gene. Am J Hum Genet 86(1):83–87. doi:10.1016/j.ajhg.2009.12.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Horvath A, Mericq V, Stratakis CA (2008) Mutation in PDE8B, a cyclic AMP-specific phosphodiesterase in adrenal hyperplasia. N Engl J Med 358(7):750–752. doi:10.1056/NEJMc0706182

    Article  CAS  PubMed  Google Scholar 

  38. McLachlan SM, Rapoport B (2004) Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies? Thyroid 14(7):510–520. doi:10.1089/1050725041517057

    Article  CAS  PubMed  Google Scholar 

  39. Mustapha M, Chouery E, Chardenoux S, Naboulsi M, Paronnaud J, Lemainque A, Megarbane A, Loiselet J, Weil D, Lathrop M, Petit C (2002) DFNB31, a recessive form of sensorineural hearing loss, maps to chromosome 9q32-34. Eur J Hum Genet 10(3):210–212. doi:10.1038/sj.ejhg.5200780

    Article  CAS  PubMed  Google Scholar 

  40. Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K, Gibbs RA, Butte NF (2012) Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PLoS One 7(12):e51954. doi:10.1371/journal.pone.0051954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rull A, Camps J, Alonso-Villaverde C, Joven J (2010) Insulin resistance, inflammation, and obesity: role of monocyte chemoattractant protein-1 (or CCL2) in the regulation of metabolism. Mediat Inflamm. doi:10.1155/2010/326580

    Google Scholar 

  42. Jiang Y, Zhang H (2011) Propensity score-based nonparametric test revealing genetic variants underlying bipolar disorder. Genet Epidemiol 35(2):125–132. doi:10.1002/gepi.20558

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rocanin-Arjo A, Cohen W, Carcaillon L, Frere C, Saut N, Letenneur L, Alhenc-Gelas M, Dupuy AM, Bertrand M, Alessi MC, Germain M, Wild PS, Zeller T, Cambien F, Goodall AH, Amouyel P, Scarabin PY, Tregouet DA, Morange PE, CardioGenics C (2014) A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential. Blood 123(5):777–785. doi:10.1182/blood-2013-10-529628

    Article  CAS  PubMed  Google Scholar 

  44. Williams FM, Carter AM, Hysi PG, Surdulescu G, Hodgkiss D, Soranzo N, Traylor M, Bevan S, Dichgans M, Rothwell PM, Sudlow C, Farrall M, Silander K, Kaunisto M, Wagner P, Saarela O, Kuulasmaa K, Virtamo J, Salomaa V, Amouyel P, Arveiler D, Ferrieres J, Wiklund PG, Ikram MA, Hofman A, Boncoraglio GB, Parati EA, Helgadottir A, Gretarsdottir S, Thorsteinsdottir U, Thorleifsson G, Stefansson K, Seshadri S, DeStefano A, Gschwendtner A, Psaty B, Longstreth W, Mitchell BD, Cheng YC, Clarke R, Ferrario M, Bis JC, Levi C, Attia J, Holliday EG, Scott RJ, Fornage M, Sharma P, Furie KL, Rosand J, Nalls M, Meschia J, Mosely TH, Evans A, Palotie A, Markus HS, Grant PJ, Spector TD, Euro CI, Wellcome Trust Case Control C, Monica Risk GA, Monograph, MetaStroke, International Stroke Genetics C (2013) Ischemic stroke is associated with the ABO locus: the EuroCLOT study. Ann Neurol 73(1):16–31. doi:10.1002/ana.23838

    Article  PubMed  PubMed Central  Google Scholar 

  45. Petros S, Kliem P, Siegemund T, Siegemund R (2012) Thrombin generation in severe sepsis. Thromb Res 129(6):797–800. doi:10.1016/j.thromres.2011.08.004

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Split, Split, Croatia

    A. Barić, S. Gračan, V. Torlak Lovrić, M. Šimunac, M. Brekalo & A. Punda

  2. Department of Medical Biology, School of Medicine, University of Split, Split, Croatia

    L. Brčić, I. Gunjača, M. Barbalić, T. Zemunik & V. Boraska Perica

  3. Department of Pharmacology, School of Medicine, University of Split, Split, Croatia

    M. Boban

  4. Department of Public Health, School of Medicine, University of Split, Split, Croatia

    O. Polašek

Authors
  1. A. Barić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Brčić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Gračan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. Torlak Lovrić
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. Gunjača
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Šimunac
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Brekalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Boban
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. O. Polašek
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Barbalić
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T. Zemunik
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A. Punda
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. V. Boraska Perica
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Boraska Perica.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest associated with the manuscript. The formation of HT biobank was supported by the Croatian Science Foundation under the project “Genome-wide association analysis of Hashimoto thyroiditis” (Grant No. 4950). The 10,001 Dalmatians project was supported by the MRC Human Genetics Unit, The Croatian Ministry of Science, Education and Sports (Grant 216-1080315-0302), the European Union Framework Program 6 EUROSPAN project (Contract No. LSHG-CT-2006-018947), EU FP7 BBMRI-LPC (Biobanking and biomolecular resources research infrastructure—Large prospective cohort, contract 313010) and the Croatian Science Foundation (Grant 8875). Measurement of thyroid hormones and antibodies in the 10,001 Dalmatians cohort was supported by the Croatian Science Foundation (Grant No. 1498).

Ethical Standards

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barić, A., Brčić, L., Gračan, S. et al. Association of established hypothyroidism-associated genetic variants with Hashimoto’s thyroiditis. J Endocrinol Invest 40, 1061–1067 (2017). https://doi.org/10.1007/s40618-017-0660-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-017-0660-8

Keywords

Search

Navigation