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Genetic and environmental factors in the aetiology of simple goitre.
Annals of Medicine 2000 April
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.
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