The LOC387715 gene, smoking, body mass index, environmental associations with advanced age-related macular degeneration.
OBJECTIVE
Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. It is now evident that both genetic and environmental factors contribute to disease susceptibility. We tested the hypotheses that (a) a common coding SNP in the LOC387715 gene is associated with advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that modifiable environmental exposures alter AMD susceptibility associated with this SNP.


METHODS
A case-control association analysis was performed on participants (530 advanced AMD cases and 280 controls) ascertained as part of the multi-center Age-Related Eye Disease Study. AMD status was determined by the reading center from fundus photographs using the AREDS AMD grading categorization. Environmental risk factor exposure data was collected from participants whose DNA was also genotyped for the LOC387715 gene SNP rs10490924. Multivariate logistic regression analyses were performed.


CONCLUSIONS
The number of risk alleles at the LOC387715 SNP was associated with advanced AMD, with odds ratios (OR) = 3.0 (95% confidence interval (CI) 2.1-4.3) for the GT heterozygous genotype and OR = 12.1 (5.6-26.5) for the homozygous TT risk genotype, after controlling for demographic and behavioral risk factors. The LOC387715 SNP was associated with both forms of advanced AMD. Current cigarette smoking and body mass index were independently related to AMD, controlling for genotype. However, there was no statistical interaction between LOC387715 genotype and smoking with regard to advanced AMD development.
Francis
Peter J
PJ
Macular Degeneration Center, Casey Eye Institute, Oregon Health and Science University, Portland, OR 97239, USA.
George
Sarah
S
Schultz
Dennis W
DW
Rosner
Bernard
B
Hamon
Sara
S
Ott
Jurg
J
Weleber
Richard G
RG
Klein
Michael L
ML
Seddon
Johanna M
JM
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
C514392:ARMS2 protein, human; D011506:Proteins