title: A high-frequency polymorphism of NADH-cytochrome b5 reductase in African-Americans.
abstract: NADH-cytochrome b5 reductase (b5R) is a member of a flavoenzyme family of dehydrogenases-electron transferases that participates in the transfer of electrons from the NADH generated in glycolysis to cytochrome b5. b5R is involved in the steady-state reduction of methemoglobin to hemoglobin in erythrocytes and is also involved in lipid metabolism in other cell types. In a search for mutations of the b5R gene in two unrelated African-American families, a high-frequency polymorphism was detected in the propositi from both families, as well as unrelated normal controls, consisting of a C-to-G transversion in exon 5 that changes threonine to serine at codon 116 (T116S). This is the first polymorphism found in the b5R gene. Using allele-specific PCR on the two propositi, their family members, and unselected populations of African-American, Caucasian, Asian, Indo-Aryan, and Arabic individuals, the C/G polymorphism was found in 26 of 112. African-American chromosomes (allele frequency = 0.23), but not in 108 Caucasian, 46 Asian, 44 Indo-Aryan, or 14 Arabic chromosomes. In preliminary studies, this polymorphism did not correlate with b5R enzyme activity or cause any disease phenotype. It remains to be determined whether this African-specific polymorphism that apparently originated recently in human evolution provides any special survival advantage.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Jenkins
authors.forename: J T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D001741:Black or African American; D000483:Alleles; D044383:Black People / Q000235:genetics*; D003579:Cytochrome Reductases / Q000235:genetics*; D042966:Cytochrome-B(5) Reductase; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase