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  • Title: Aggregation of thyroid autoantibodies in first-degree relatives of patients with autoimmune thyroid disease is mainly due to genes: a twin study.
    Author: Brix TH, Hansen PS, Kyvik KO, Hegedüs L.
    Journal: Clin Endocrinol (Oxf); 2004 Mar; 60(3):329-34. PubMed ID: 15008998.
    Abstract:
    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. AIM: To test the hypothesis that the familial aggregation of thyroid autoantibodies is mainly genetically determined. DESIGN: A cross-sectional study of healthy twin siblings to twins with AITD. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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). CONCLUSION: 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.
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