THE RELATIONSHIP OF THE -5, -8, AND -24 VARIANT ALLELES IN AFRICAN-AMERICANS TO TRIOSEPHOSPHATE ISOMERASE (TPI) ENZYME-ACTIVITY AND TO TPI DEFICIENCY

In 424 African-American and 75 white subjects, we found that the -5 (T PI 592 A-->G), -8 (TPI 589 G-->A), and -24 (TPI 573 T-->G) variants in the triosephosphate isomerase (TPI) gene occurred frequently (41.0%) in the African-American subjects but did not occur in the whites. Thes e data suggest that this set of polymorphisms may turn out to be one o f the higher-incidence molecular markers of African lineage, a surpris ing finding because others had reported that these nucleotide substitu tions were restricted to a small subset of African Americans who had b een characterized as TPI-deficiency heterozygotes. Additionally, we in vestigated the relationship of these variants to TPI-enzyme activity. Although the variant substitutions (occurring in three haplotypes: -5 alone, -5 -8, and -5 -8 -24) were associated with moderate reduction i n enzyme activity, severe-deficiency heterozygotes could not be identi fied with certainty, and none of the haplotypes were restricted to sub jects with marked reduction of enzyme activity. Three subjects were ho mozygous for the -5 -8 haplotype, a finding inconsistent with the puta tive role of this haplotype as the cause of a null variant incompatibl e with life in homozygotes. Despite these findings, the possibility re mains that the -5 -8 or -5 -8 -24 haplotypes may in some instances con tribute to compound heterozygosity and clinical TPI deficiency. (C) 19 98 by The American Society of Hematology.