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 (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.
Department of Pathology, Finch University of Health Sciences/The Chicago Medical School, North Chicago, IL, USA. schneidr@finchcms.edu
A
A
Schneider
L
L
Forman
B
B
Westwood
C
C
Yim
J
J
Lin
S
S
Singh
E
E
Beutler
D000483:Alleles; D044383:Black People / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D014305:Triose-Phosphate Isomerase / Q000172:deficiency / Q000235:genetics*; D044465:White People / Q000235:genetics; D001741:Black or African American
D014305:Triose-Phosphate Isomerase