Glutathione S-transferase omega-2 polymorphism Asn142Asp modifies the risk of age-related cataract in smokers and subjects exposed to ultraviolet irradiation.
BACKGROUND
Glutathione S-transferase omega-1 and 2 have a unique range of enzymatic activities, including the regeneration of ascorbate by their dehydroascorbate reductase activities. Because these enzymes could have a protective role from oxidative damage in the lens, the question of whether the two coding glutathione S-transferase omega polymorphisms confer the risk of age-related cataract was addressed.


METHODS
rs4925 (Ala140Asp) of glutathione S-transferase omega-1 and rs156697 (Asn142Asp) of glutathione S-transferase omega-2 polymorphisms in 100 patients with age-related cataract and 130 controls were assessed.


RESULTS
Presence of one mutant GSTO1*Asp or GSTO2*Asp allele did not contribute independently towards the risk of cataract; however, homozygous carriers of GSTO1*Asp/GSTO2*Asp haplotype demonstrated 3.42-fold enhanced risk of cataract development (95% confidence interval = 0.84-13.93; P = 0.086). When GSTO genotype was analysed in association with smoking or professional exposure to ultraviolet irradiation, carriers of at least one mutant GSTO2*Asp allele had increased risk of cataract development in comparison with individuals with wild-type GSTO2*Asn/Asn with no history of smoking or ultraviolet exposure (odds ratio = 6.89, 95% confidence interval = 1.81-16.21, P = 0.005; odds ratio = 4.10, 95% confidence interval = 1.23-13.74, P = 0.022, respectively). Regarding the distribution of particular glutathione S-transferase omega genotype and cataract type, the highest frequency of mutant GSTO2*Asp allele was found in patients with nuclear cataract.


CONCLUSIONS
The results indicate that mutant GSTO2*Asp genotype is associated with increased risk of age-related cataract in smokers and ultraviolet-exposed subjects, suggesting a role of inefficient ascorbate regeneration in cataract development.
Medical Center Zvezdara, University Eye Clinic, Belgrade, Serbia; Faculty of Special Education and Rehabiltation, University of Belgrade, Belgrade, Serbia.
Miroslav
M
Stamenkovic
Tanja
T
Radic
Ivan
I
Stefanovic
Vesna
V
Coric
Ivan
I
Sencanic
Marija
M
Pljesa-Ercegovac
Marija
M
Matic
Vesna
V
Jaksic
Tatjana
T
Simic
Ana
A
Savic-Radojevic
D000368:Aged; D000375:Aging; D000483:Alleles; D002386:Cataract / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007908:Lens, Crystalline / Q000528:radiation effects*; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011832:Radiation Injuries / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
C490476:GSTO1 protein, human; C492569:GSTO2 protein, human; D005982:Glutathione Transferase
GSTO gene; association; disease risk