ABSTRACT
Manganese Superoxide Dismutase 15
MnSOD Background 15
MnSOD Polymorphisms 16
MnSOD and Health Conditions 17
Late-Onset Neurological Disorders 17
Cancer 17
Copper, Zinc Superoxide Dismutase 18
SOD3 Background 19
SOD3 Polymorphisms 19
The Glutathione-S-Transferases 19
The GST Genes 20
GSTM1-Glutathione-S-Transferase M1 20
GSTM1 Background 20
GSTM1 Biomarkers 21
GSTM1 and Health Conditions 21
Glutathione-S -Transferase P1 22
GSTP1 Background 23
GSTP1 Biomarkers 23
GSTP1 and Health Conditions 23
Glutathione-S-Transferase T1 24
GSTT1 Biomarkers 24
GSTT1 and Health Conditions 24
Cancer 24
Endothelial Nitric Oxide Synthase 25
eNOS Summary 25
Functional Studies of the 894G . T (Glu298Asp) Polymorphism 25 eNOS Glu298Asp (G . T) and Cardiovascular Disease 26 eNOS and Oxidative Stress of Smokers 26
Potential Dietary Interventions 26
Catalase 27
CAT Background 27
CAT Polymorphisms 27
NADPH Oxidase 28
NADPH Oxidase Background 28
NADPH Polymorphisms 28
NADPH Polymorphisms and Health Conditions 28
Glutathione Peroxidase 29
GPX1 Background 29
GPX1 Polymorphisms 29
GPX1 Polymorphisms and Health 29
Myeloperoxidase 30
MPO Background 30
MPO Polymorphisms 30
NADPH Dehydrogenase, Quinone 1 31
NADPH Background 31
NADPH Polymorphisms 31
Conclusion 31
References 32
Oxidative stress has been attributed to a host of human disorders ranging from
cancer to premature aging. Although the role of oxidative stress in damaging
tissues ultimately leading to disease or disrepair is widely accepted, science is
progressing rapidly in terms of understanding the impact of interindividual vari-
ation in genes responsible for dealing with oxidative stress in cells. As molecular
techniques have advanced and the technology has become more accessible, it has
become much easier to include analysis of genetic variation in epidemiological
studies as well as biochemical studies modeling particular genetic variations.
Single nucleotide polymorphisms (snps) are the most common variations that
exist in the human genome, occurring at 1500 bp intervals in the human genome. Snps are considered distinct from rare mutations in that a snp by
definition must occur in at least 1% of the population. Many of these sequence
alterations may occur in noncoding regions of the genome, and may have no
significance, others may lead to alterations in the amino acid sequence of the
gene product, leading to a functional change in the protein, still others may
alter the promoter region, thus having an impact on efficiency of transcription
of the gene. Often, snps are identified through molecular epidemiological
methods that do not have a clear functional effect, and these variations are
assumed to be in linkage disequilibrium with some other, yet unidentified func-
tional variation. Other variations that can occur include insertions and deletions,
in one common example, the complete sequence of the GSTM1 gene, for
example, is deleted in 50% of the Caucasian population. Useful online resources for studying human variation include the Database of Single Nucleo-
tide Polymorphisms https://www.ncbi.nlm.nih.gov/SNP, GeneCards https:// bioinformatics.weizmann.ac.il/cards, the Human Gene Mutation Database https://archive.uwcm.ac.uk/uwcm/mg/hgmd0.html, OMIM (Online Mendelian Inheritance in Man) https://www.ncbi.nlm.nih.gov/OMIM, and the SNP consortium https://snp.cshl.org.
