Affordable Access

The relationship of the -5, -8, and -24 variant alleles in African Americans to triosephosphate isomerase (TPI) enzyme activity and to TPI deficiency.

Authors
  • Schneider, A
  • Forman, L
  • Westwood, B
  • Yim, C
  • Lin, J
  • Singh, S
  • Beutler, E
Type
Published Article
Journal
Blood
Publication Date
Oct 15, 1998
Volume
92
Issue
8
Pages
2959–2962
Identifiers
PMID: 9763583
Source
Medline
License
Unknown

Abstract

In 424 African-American and 75 white subjects, we found that the -5 (TPI 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. These data suggest that this set of polymorphisms may turn out to be one of the higher-incidence molecular markers of African lineage, a surprising finding because others had reported that these nucleotide substitutions were restricted to a small subset of African Americans who had been characterized as TPI-deficiency heterozygotes. Additionally, we investigated 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 in enzyme activity, severe-deficiency heterozygotes could not be identified with certainty, and none of the haplotypes were restricted to subjects with marked reduction of enzyme activity. Three subjects were homozygous for the -5 -8 haplotype, a finding inconsistent with the putative role of this haplotype as the cause of a null variant incompatible with life in homozygotes. Despite these findings, the possibility remains that the -5 -8 or -5 -8 -24 haplotypes may in some instances contribute to compound heterozygosity and clinical TPI deficiency.

Report this publication

Statistics

Seen <100 times