Association of CT60 cytotoxic T lymphocyte antigen-4 gene polymorphism with thyroid autoantibody production in patients with Hashimoto's and postpartum thyroiditis.
Strong genetic contribution has been demonstrated to influence the development of autoimmune thyroid disease (AITD) as well as thyroid autoantibody production. In order to assess the relation between CT60 cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism and thyroid autoantibody production, we investigated 180 consecutive newly diagnosed patients with two forms of AITD, 105 with Hashimoto's thyroiditis (HT) and 75 with postpartum thyroiditis (PPT). We evaluated thyroid function, measured antibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg), and determined CT60 CTLA-4 gene polymorphism. In HT, TPO antibody median value was significantly lower in the AA compared to the AG and GG genotypes (65, 122 and 319 U/ml, P<0.005), while the Tg antibody median value was lower in the AA compared to the AG genotype (91 and 189 U/ml, P<0.02). In PPT, the frequency of thyroid autoantibody-positive patients was higher among G-allele-carrying genotypes (P<0.04). Similar to HT, the TPO antibody median value was lower in the AA compared to the AG and GG genotypes (12, 130 and 423 U/ml, P<0.006). Hypothyroid PPT patients were more often thyroid autoantibody-positive (P<0.005) and the TPO antibody median value was higher compared to hyperthyroid PPT patients (500 and 32 U/ml, P<0.0001). The frequency of the G-allele was significantly higher among hypothyroid patients (P<0.05). Our data suggest that in both HT and PPT, the CT60 CTLA-4 gene polymorphism contributes importantly to thyroid autoantibody production. In PPT, the genotype also seems to influence thyroid function, as patients with the polymorphous allele are more prone to develop hypothyroid form of PPT.
Zaletel
K
K
Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia. katja.zaletel@kclj.si
Krhin
B
B
Gaberscek
S
S
Bicek
A
A
Pajic
T
T
Hojker
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D060908:CTLA-4 Antigen; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D050031:Hashimoto Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology / Q000235:genetics / Q000276:immunology; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050032:Postpartum Thyroiditis / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy; D013954:Thyroglobulin / Q000276:immunology; D055815:Young Adult
D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C006606:anti-thyroglobulin; C056626:thyroid microsomal antibodies; D013954:Thyroglobulin; D007453:Iodide Peroxidase
Genes Immun. 2001 May;2(3):145-52
11426323
BMC Med Genet. 2007 Feb 06;8:3
17280620
Immunogenetics. 2002 Apr;54(1):1-8
11976786
Clin Exp Immunol. 1967 Dec;2:Suppl:719-25
5590107
Thyroid. 2002 May;12(5):373-6
12097196
Genes Immun. 2002 Jun;3(4):233-4
12058260
J Clin Endocrinol Metab. 2000 Sep;85(9):3191-8
10999807
Autoimmunity. 2005 Mar;38(2):151-3
16040335
Clin Endocrinol (Oxf). 1998 Aug;49(2):251-5
9828915
Thyroid. 2004 Aug;14(8):610-5
15320974
J Autoimmun. 2007 Mar-May;28(2-3):85-98
17369021
Neuro Endocrinol Lett. 2008 Jun;29(3):334-40
18580850
Clin Endocrinol (Oxf). 2003 Sep;59(3):396-401
12919165
J Immunol. 2000 Dec 1;165(11):6606-11
11086105
Genes Immun. 2003 Dec;4(8):586-93
14647199
Eur J Endocrinol. 2006 Jan;154(1):29-38
16381988
J Clin Endocrinol Metab. 1990 Mar;70(3):742-6
2307728
J Biol Chem. 2002 Nov 29;277(48):46478-86
12244107
Nature. 2003 May 29;423(6939):506-11
12724780
J Clin Endocrinol Metab. 2006 Mar;91(3):1087-92
16352685
J Clin Endocrinol Metab. 2001 Apr;86(4):1687-93
11297604
Int J Immunogenet. 2006 Apr;33(2):87-91
16611252
Eur J Endocrinol. 2003 Jan;148(1):1-9
12534350
J Clin Endocrinol Metab. 2007 Aug;92(8):3162-70
17504905
J Clin Endocrinol Metab. 2004 Dec;89(12):6257-65
15579786
J Autoimmune Dis. 2005 Oct 31;2:8
16259622
Thyroid. 2006 Jun;16(6):573-82
16839259
J Clin Endocrinol Metab. 2000 Jan;85(1):71-5
10634366
Clin Endocrinol (Oxf). 2004 Mar;60(3):329-34
15008998
Thyroid. 2007 Oct;17(10):963-73
17900225
Eur J Endocrinol. 1998 Jul;139(1):36-43
9703376
J Clin Endocrinol Metab. 2008 Sep;93(9):3589-96
18559906
Thyroid. 2002 May;12(5):377-80
12097197
Thyroid. 2003 Mar;13(3):297-300
12729480
Hum Immunol. 2009 Oct;70(10):820-4
19559744