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BRIX
Genetic and environmental causes of individual differences in thyroid size: a study of healthy Danish twins.Hansen PS, Brix TH, Bennedbaek FN, Bonnema SJ, Kyvik KO, Hegedus L. J Clin Endocrinol Metab. 2004 May;89(5):2071-7.
"OBJECTIVE: In euthyroid individuals, autoantibodies to thyroid peroxidase (TPOab) and thyroglobulin (Tgab) are regarded as early markers of thyroid autoimmunity. Family and twin studies suggest that development of thyroid autoantibodies in first-degree relatives of patients with autoimmune thyroid disease is under genetic influence. We aimed to estimate the relative importance of genetic and environmental effects for the presence of thyroid autoantibodies in euthyroid subjects. METHODS: A representative sample of healthy twin pairs was identified through the Danish Twin Registry; 1372 individuals, divided into 283 monozygotic (MZ), 285 dizygotic same sex (DZ), and 118 opposite sex twin pairs were investigated. Serum TPOab and serum Tgab were measured. Proband-wise concordance and intraclass correlations were calculated, and quantitative genetic modelling was performed. RESULTS: Probandwise concordance and intraclass correlations were consistently higher for MZ than for DZ twin pairs indicating genetic influence. Genetic components (with 95% confidence intervals) accounted for 73% (46-89%) of the liability of being thyroid antibody positive. Adjusting for covariates (age, TSH and others), the estimate for genetic influence on serum TPOab concentrations was 61% (49-70%) in males and 72% (64-79%) in females. For serum Tgab concentrations, the estimates were 39% (24-51%) and 75% (66-81%) respectively. CONCLUSIONS: Early markers of thyroid autoimmunity appear to be under strong genetic influence. The analyses suggest that it is the same set of genes that operate in males and females. However, complex mechanisms such as dominance and/or epistasis may be involved."
Genetic and environmental factors in the aetiology of simple goitre.Brix
TH, Hegedus L. [abstract only]
"The aetiology of simple goitre, affecting up to 5% of a population in iodine-sufficient areas and over 10% in endemic areas, is incompletely understood. It is generally believed that the development of simple goitre, whether endemic or sporadic, depends on complex interactions between genetic, environmental and endogenous factors. The importance of genetic factors is evident from the clustering of simple goitre within families and from a higher concordance rate for goitre in monozygotic than in dizygotic twins. Recently, studies assessing the role of specific candidate genes or genetic markers in the aetiology of simple goitre have given conflicting data in various families. However, there may well be single genes playing a major role within certain families, eg the thyroglobulin (Tg) gene, the thyroid-stimulating hormone receptor (TSHR) gene, the Na+/I- symporter (NIS) gene, and the multinodular goitre marker 1 (MNG1) on chromosome 14, but the genes will vary from family to family. In addition, family and twin studies also indicate a modest to major role for environmental factors in the aetiology of simple goitre. Clearly, iodine deficiency and cigarette smoking are the most important environmental risk factors associated with the genesis of simple goitre. Other suggested risk factors include naturally occurring goitrogens, emotional stress and certain drugs and infections. Ongoing studies focus on whole-genome screening in multiplex families as well as on large population-based case-control studies. However, the possibility that simple goitre is a heterogeneous disease without a single well-defined genotype and phenotype should be left open."
Major role of genes in the etiology of simple goiter in females: a population-based twin study.Brix
TH, Kyvik KO, Hegedus L.
"The etiology of simple goiter, affecting up to 5% of a population in nonendemic areas, is incompletely understood. It is generally believed to be multifactorial in origin, but the relative contributions of genetic and environmental factors remain to be clarified. Therefore, we investigated a well defined population of Danish twins. We performed a historical cohort study of 5.479 same sex twin pairs born between 1953 and 1972. Information on goiter was obtained from a nationwide questionnaire survey in 1994. Information from hospitals, out-patient clinics, and the subjects' general practitioners was sought to verify the diagnoses. Concordance rates, tetrachoric correlations, and heritability were determined. The crude probandwise concordance rates were 0.42 [95% confidence interval (CI), 0.26-0.591 and 0.13 (95% CI, 0.06-0.24) for female monozygotic and female dizygotic pairs, respectively. The age-adjusted cumulative probandwise risk for simple goiter from birth to age 43 yr was 0.53 (95% CI, 0.23-0.83) for female monozygotic twins and 0.18 (95% CI, 0.05-0.35) for female dizygotic twins (P = 0.003). The tetrachoric correlations were substantially higher in monozygotic (0.82; SE, 0.07) than in dizygotic twins (0.47; SE, 0.12). Model-fitting analysis suggested that the heritability of the liability to the development of simple goiter in women is approximately 82%. Individual-specific environmental factors not shared by cotwins seemed to explain the remaining 18%. We conclude that the etiology of clinically overt simple goiter is multifactorial. Genetic factors play a major role in the etiology of simple goiter in females, but environmental factors are also of importance."
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