Abstract
BackgroundThe SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. SOD2 polymorphisms are of interest because of their potential roles in the modulation of free radical-mediated macromolecular damage during aging.ResultsWe identified a new splice variant of SOD2 in human lymphoblastoid cell lines (LCLs). The alternatively spliced product was originally detected by exon trapping of a minigene in order to examine the consequences of an intronic polymorphism found upstream of exon 4 (nucleotide 8136, 10T vs 9T). Examination of the transcripts derived from the endogenous loci in five LCLs with or without the intron 3 polymorphism revealed low levels of an in-frame deletion of exon 4 that were different from those detected by the exon trap assay. This suggested that exon trapping of the minigene unmasked the effect of the 10T vs 9T polymorphism on the splicing of the adjacent exon.We also determined the frequencies of single nucleotide polymorphisms in a sample of US African-Americans and non-African-Americans ages 65 years and older who participated in the 1999 wave of the National Long Term Care Survey (NLTCS). Particularly striking differences between African-Americans and non-African-Americans were found for the frequencies of genotypes at the 10T/9T intron 3 polymorphism.ConclusionExon trapping can unmask in vitro splicing differences caused by a 10T/9T intron 3 polymorphism. Given the recent evidence that SOD2 is in a region on chromosome 6 linked to susceptibility to hypertension, it will be of interest to investigate possible associations of this polymorphism with cardiovascular disorders.
Highlights
The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase
The 1999 National Long Term Care Survey (NLTCS) populations DNA was obtained from a total of 644 blood samples
Because a striking difference in the frequencies for the polymorphism at the nucleotide position 8,136 was observed among African-Americans, studies of that polymorphism were extended to the larger sample of genomic DNA from buccal samples
Summary
The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. The free radical theory of aging is currently the leading hypothesis for a fundamental mechanism of aging. It potentially unifies aging mechanisms across an array of species [1,2,3,4,5]. The theory postulates that reactive oxygen species (ROS) such as superoxide and hydroxyl radicals, mainly generated as toxic by-products of normal cellular metabolism during aerobic respiration in mitochondria, give rise to damage to wide variety of macromolecules, including DNA. Among the most important of such antioxidant defenses are the superoxide dismutases (SOD), which facilitate the dismutation of superoxide free radical (O2-.) [6]. There are three types of SODs in higher eukaryotes, a copper/zinc containing cytoplasmic enzyme, SOD1; a manganese containing mitochondrial enzyme, SOD2; and a copper/zinc containing SOD3 that is prevalent in extracellular spaces [6,7]
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