Endocrine Abstracts

Association of CTLA-4 exon 1 polymorphism with Graves’ disease in Spanish patients

P Álvarez-Vázquez, D Valverde, L Constela, L Pérez Méndez & RV García-Mayor

University Hospital of Vigo, Vigo, Spain.

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Introduction: Graves disease (GD) is inherited as a complex multigenic disorder. One of the most promising genes for susceptibility to GD is cytotoxic T lymphocyte antigen-4 (CTLA4), a negative regulator of T-cell activation.

Objective: The aim of this study was to determine whether A/G polymorphism in exon 1 of the CTLA-4 gen was associated with GD in spanish patients.

Patients and methods: Fifty one adult GD patients and 25 unrelated controls were analyzed. GD was defined as hyperthyroidism together with following criteria: diffuse goiter, thyroglobulin and/or thyroid peroxidase abs and/or ophthalmopathy. Polymorphism were analyzed using a restriction enzyme digestion with BbvI of polymerasa chain reaction (PCR) amplified genomic.

Results: Forty three women (84%) in the total of 51 patients studied. The medium age was 41,25 years (18–75). The distribution of genotype frequencies and the frequencies of the A and G alleles differed between GD subjects and controls (see table). In the control group we have not detected homozygous for the G allele.

A49G Mutation	Graves	Controls	P
Genotype Distribution
A/A	21 (41)	24 (58)	ns
A/G	18 (35)	21 (42)	ns
G/G	12 (24)	0	0.005
Alleles Frequency
A	30 (59)	41 (82)	0.01
G	21 (41)	11 (22)	0.04

Conclusions: Our data show that G-carrying genotypes of polymorphism CTLA4 A/G are associated with increase in risk of GD in our region. The G allele and the GG genotype were increased among Spanish patients. We not found association between AG genotype and GD like other previous studies in Caucasian patients. CTLA-4 polymorphism varies according to ethnic group and environmental variables and it is important its identification than in future can influence the selection of treatment of GD.

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Endocrine Abstracts (2006) 11 P817