Isoelectric focusing variant thyroxine-binding globulin in American blacks: increased heat lability and reduced serum concentration.

Three major bands of T4-binding globulin (TBG) at pH 4.3-4.5 are seen after isoelectric focusing (IEF) of serum. Daiger et al. detected a cathodal shift of all IEF bands in some American blacks, and found that the inheritance of this variant TBG (TBG-S) is X-chromosome linked. However, the properties of the TBG-S molecule and its possible association with changes in thyroid function have not been studied. Based on IEF analysis of 114 serum samples from adult American blacks, the gene frequency of TBG-S was 12.0%, and the genotype distribution was consistent with X-chromosomal linkage. TBG-S and the common type TBG (TBG-C) co-occurred exclusively in sera from women, whereas sera from men had only TBG-C or TBG-S, confirming the X-linked inheritance of this variant TBG. At 60 C, TBG-S was denatured with a mean t1/2 of 4.7 +/- 0.9 (+/-SD) min compared to 6.8 +/- 1.1 min for TBG-C (P less than 0.001). Heterozygous females with TBG-CS had an intermediate rate of heat denaturation (t1/2, 5.2 +/- 0.7 min). In vitro mixtures of TBG-S and TBG-C also had intermediate t1/2 values, indicating that the heat lability of TBG-S is inherent to the variant TBG molecule. Heat denaturation resulted in loss of T4-binding activity, which was proportional among corresponding IEF bands for each of the two TBG types. Larger amounts of added T4 were required to protect against the heat-induced denaturation of TBG-S. No changes in the affinity of TBG-S for T4 could be demonstrated by analysis of binding kinetics at O C. Thyroid function tests were carried out in 10 black men with TBG-S and 10 age-matched black men with TBG-C. The mean concentration of total T4 (TT4) of 6.8 +/- 1.5 micrograms/dl in the group of TBG-S men was lower (P less than 0.02) than that in the group of TBG-C men (8.5 +/- 1.3 micrograms/dl). The finding of lower levels of TT4 in men with TBG-S was best explained on the basis of a concomitant reduction of serum TBG concentration (1.41 +/- 0.30 vs. 1.72 +/- 0.23 mg/dl; P less than 0.05). This conclusion was confirmed when no significant difference in mean TT4 concentration was found between the group with TBG-S and another with TBG-C matched by serum TBG concentration.(ABSTRACT TRUNCATED AT 400 WORDS)