MOLECULAR CHARACTERIZATION OF A GENETIC VARIANT OF THE STEROID HORMONE-BINDING GLOBULIN GENE IN HETEROZYGOUS SUBJECTS

Steroid hormone-binding globulin in human serum displays different iso electric focusing (IEF) patterns among individuals, suggesting genetic variation in the gene for this extracellular steroid carrier protein. Analysis of allele frequencies and family studies suggested the exist ence of two codominant alleles of the gene. Subsequent determination o f the molecular basis of a variant of the gene was carried out using D NA from homozygous individuals from a single Belgian family. It was of interest to characterize other variant individuals to determine wheth er all variants identified by IEF phenotyping were caused by the same mutation or whether other mutations occurred in the gene in different populations. Previous studies identified Mexican subjects who were het erozygous for the variant IEF phenotype. Denaturing gradient gel elect rophoresis was used to localize the mutation in these subjects and to purify the variant allele for DNA sequence analysis. The results show that the mutation in this population is identical to that identified i n the Belgian family, and no other mutations were detected in the gene . These data represent the first analysis of steroid hormone-binding g lobulin gene variation in heterozygous subjects and further support th e conclusion of biallelism of the gene worldwide.