A possible variant of thyroxine-binding globulin in Australian Aborigines

We have recently described a major variation from the normal levels of serum thyroxine-binding globulin in many Australian Aborigines [1]. Subsequently we presented evidence that affected individuals were widely distributed throughout Australia, that "low values of thyroxine-binding globulin were not caused by environmental or health factors, but were inherited in an autosomal dominant fashion [2]. Refetoff [3] has shown that the cause of genetically determined low thyroxine-binding globulin levels in Caucasians is alteration in synthesis rate without any structural variation of the protein. Since however the "low" thyroxine-binding globulin of Aborigines is vastly more prevalent and genetically distinct from the X-linked type, we investigated the possibility that this may be a structural variant. Evidence suggestive of this includes results from heat inactivation, competitive binding of thyroxine to thyroxine-binding globulin to measure affinity, and use of a radioimmunoassay different from that used in the original work. The "Low thyroxine-binding globulin of Aborigines may be a protein with a structural variation at or near the binding site for thyroxine, resulting in low affinity for thyroxine and hence "low" results with assay methods which depend upon the thyroxine binding site. Since the Australoid peoples, to whom Australian Aborigines are racially related, are distributed widely throughout the southern hemisphere it is important to establish whether this variant is found outside Australia in order to avoid the likelihood of misdiagnosis of thyroid disease in such subjects.