Aggregation of thyroid autoantibodies in first-degree relatives of patients with autoimmune thyroid disease is mainly due to genes: a twin study.
BACKGROUND
Family studies have repeatedly shown aggregation of thyroid autoantibodies to thyroid peroxidase (TPOab) and thyroglobulin (Tgab) in first-degree relatives of patients with autoimmune thyroid disease (AITD). This phenomenon has generally been interpreted as evidence of a genetic component in the development of thyroid autoantibodies. However, family studies cannot determine whether the observed familial aggregation of these antibodies is due to shared genes or shared environment.


OBJECTIVE
To test the hypothesis that the familial aggregation of thyroid autoantibodies is mainly genetically determined.


METHODS
A cross-sectional study of healthy twin siblings to twins with AITD.


METHODS
Thirty-eight healthy twin siblings to twins with AITD and a control group of 76 healthy twins, matched for age, sex and zygosity, but without AITD among their first-degree relatives.


METHODS
Prevalence of TPOab, Tgab and TSH-receptor antibodies (TSHRab).


METHODS
All antibodies were measured by routine commercial kits. TPOab, Tgab and TSHRab were regarded as positive if > 60 U/ml, > 60 U/ml and > 1.0 U/l, respectively. Zygosity was established by DNA fingerprinting.


RESULTS
The prevalence of TPOab, Tgab and TSHRab in the 38 healthy twin siblings was 34% (13/38), 26% (10/38) and 13% (5/38), respectively, which was higher than the corresponding prevalences in the control population, 9% (7/76; P = 0.002), 7% (5/76; P = 0.006) and 1.3% (1/76; P = 0.015), respectively. Combination of two or more thyroid autoantibodies was also significantly more common among index subjects (10/38 or 26%) than in the control group (2/76 or 3%), P = 0.0001. Among the healthy monozygotic twin siblings, 53%, 47% and 20% had TPOab, Tgab and TSHRab, respectively, compared with 22% (P = 0.045), 13% (P = 0.02) and 9% (P = 0.36), respectively, in the dizygotic twin siblings. Significantly more monozygotic twin siblings were positive for two or more autoantibodies than dizygotic twin siblings (8/15 vs. 2/23; P = 0.006).


CONCLUSIONS
Healthy first-degree relatives to patients with AITD show significant clustering of thyroid autoantibodies. Moreover, healthy monozygotic and dizygotic twin siblings to twins with AITD differ in prevalence of thyroid autoantibodies. These observations strongly support the hypothesis that the familial aggregation of thyroid autoantibodies is mainly genetically determined.
Department of Endocrinology M, Odense University Hospital, Denmark. tbrix@health.sdu.uk
Thomas Heiberg
TH
Brix
Pia Skov
PS
Hansen
Kirsten Ohm
KO
Kyvik
Laszlo
L
Hegedüs
D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D004200:Diseases in Twins / Q000235:genetics*; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013963:Thyroid Hormones / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology
D001323:Autoantibodies; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D013954:Thyroglobulin; D007453:Iodide Peroxidase