Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration.
OBJECTIVE
To elucidate whether any polymorphic genes for xenobiotic-metabolizing and antioxidant enzymes are associated with the development of exudative age-related macular degeneration.


METHODS
A hospital-based case-control study was performed on a consecutive series of 102 Japanese patients with the exudative form of age-related macular degeneration who were recruited between 1993 and 1998 in the Kagoshima University Hospital. Controls were 200 systemically healthy individuals who had no senescent ocular disorders and were over 50 years of age. There was no evidence of age-related macular degeneration in the 200 controls. Genomic DNA from peripheral bloods was examined using polymerase chain reaction and defined for the genetic polymorphisms of cytochrome P-450 1A1, glutathione S-transferases, microsomal epoxide hydrolase, and manganese superoxide dismutase.


RESULTS
We found a significant association of manganese superoxide dismutase gene polymorphism, valine/alanine polymorphism at the targeting sequence of the enzyme, with age-related macular degeneration. The patients had an increased frequency of alanine allele and alanine/alanine genotype (odds ratio = 10.14, 95% confidence interval = 4.84 to 2.13; P =.0005 after Bonferroni correction). We also observed a weak association of microsomal epoxide hydrolase exon-3 polymorphism with age-related macular degeneration (odds ratio = 2.20, 95% confidence interval = 4. 02 to 1.20; P =.020 after Bonferroni correction). Cytochrome P-450 1A1, glutathione S-transferases, and microsomal epoxide hydrolase exon-4 were polymorphic, but their genotype frequency distributions did not show a statistically significant difference between the patients and controls.


CONCLUSIONS
The results suggest that manganese superoxide dismutase gene polymorphism is associated with exudative age-related macular degeneration. Microsomal epoxide hydrolase is another enzyme that may be associated with the disease. The exudative form of age-related macular degeneration may have genetic risk factors against oxidative stress and/or effects of xenobiotics. Further association studies in other polymorphic genes for xenobiotic-metabolizing enzymes are needed to elucidate the environmental-genetic interaction in the underlying cause of age-related macular degeneration.
Kimura
K
K
Department of Ophthalmology, Kagoshima University Faculty of Medicine, Sakuragaoka, Kagoshima-shi, Japan.
Isashiki
Y
Y
Sonoda
S
S
Kakiuchi-Matsumoto
T
T
Ohba
N
N
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D016166:Free Radical Scavengers; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics*
D017931:DNA Primers; D016166:Free Radical Scavengers; D004247:DNA; D019363:Cytochrome P-450 CYP1A1; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases