Variability of serum thyroglobulin levels is determined by a major gene

There are large variations in the circulating concentrations of thyroglobulin. The purpose of this study was to explore the possibility of a genetic basis for the variability of serum concentration of thyroglobulin (Tg) in euthyroid individuals.

The serum concentration of thyroglobulin (Tg) varies several-fold in euthyroid individuals. Other circulating proteins also show wide normal ranges of concentration and these variations have been shown to have a genetic as well as an environmental basis. To explore the possibility of a genetic basis for variability in serum Tg levels, an analysis was made of serum Tg levels in 44 pairs of identical twins and 66 nuclear families who were euthyroid and thyroid autoantibody negative (thereby eliminating subclinical autoimmune thyroid disease and Tg autoantibody interference with the Tg assay).

Each pair of identical twins tended to have a similar Tg level and the overall correlation was highly significant (r = 0.734, P < 0.001). There was no relation between Tg and TSH levels in the twins (r = 0.119; P = 0.366). Segregation analysis of the 66 families showed that where both parents had Tg levels above the overall median for the subjects (males, 19 micrograms/l; females, 33 micrograms/l), 73% of the offspring also had concentrations above these levels, compared with 30% of the offspring when one parent had a high Tg level and only 16% in families where neither parent had a high Tg level.

Complex segregation analysis using the computer program Pointer suggested that variability in Tg levels was the result of a major dominant-like gene effect (accounting for 80% of the variability) combined with a multifactorial component. Thyroglobulin, a template for thyroid hormone production, is also a major thyroid autoantigen and inherited variations in serum Tg levels may have implications for the pathogenesis of autoimmune thyroid disease.