The LOC387715 polymorphism, inflammatory markers, smoking, and age-related macular degeneration. A population-based case-control study.
OBJECTIVE
To assess combined effects on the risk of age-related macular degeneration (AMD) by the LOC387715 polymorphism, smoking, and inflammatory or hemostatic factors.


METHODS
Population-based case-control study.


METHODS
Two hundred seventy-eight AMD cases (224 early, 54 late) and 557 controls matched for age, gender, and smoking, drawn from the Blue Mountains Eye Study cohort.


METHODS
Subjects were genotyped for the LOC387715 Ala69Ser polymorphism (rs# 10490924). Smoking was self-reported. Serum high-sensitivity C-reactive protein (CRP), interleukin 6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), fibrinogen, homocysteine, plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor, and white cell count (WCC) were measured. Combined effects of this genetic variant plus any of these study factors on AMD risk were assessed using logistic regression models, adjusted for age and smoking. We defined interaction if the influence of 2 factors departed from the multiplicative scale, confirmed by a statistically significant interaction term. Otherwise, the combined effect was used.


METHODS
Age-related macular degeneration was graded using the Wisconsin grading system.


RESULTS
Combined effects on the likelihood of early or late AMD were demonstrated for the LOC387715 Ala69Ser G/T and T/T genotypes with the markers high-sensitivity CRP (odds ratios [ORs], 1.2 for the highest tertile alone, 1.6 for G/T and T/T genotypes alone, and 2.2 for both G/T and T/T genotypes plus the highest tertile, compared with the G/G genotype with the 2 lower tertiles), IL-6 (corresponding ORs, 1.1, 1.6, and 2.2), sICAM-1 (ORs, 1.0, 1.5, and 2.3, respectively), and PAI-1 (ORs, 1.3, 1.7, and 2.3, respectively), but not with WCC, fibrinogen, homocysteine, and von Willebrand factor. Findings were similar for early and late AMD separately. Current smokers with G/T and T/T genotypes had strong combined effects on late AMD risk compared with those who never smoked or past smokers with the G/G genotype (ORs, 1.2 for current smokers alone, 1.8 for G/T and T/T genotypes alone, and 6.1 for current smokers plus G/T and T/T genotypes).


CONCLUSIONS
We found no significant interaction but combined effects for the LOC387715 genotypes with 3 inflammatory markers and PAI-1 on the risk of early or late AMD, and with current smoking on the risk of late AMD.
Wang
Jie Jin
JJ
Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia. jiejin_wang@wmi.usyd.edu.au
Ross
Robert J
RJ
Tuo
Jingsheng
J
Burlutsky
George
G
Tan
Ava G
AG
Chan
Chi-Chao
CC
Favaloro
Emmanuel J
EJ
Williams
Andrew
A
Mitchell
Paul
P
D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008268:Macular Degeneration / Q000209:etiology* / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D018570:Risk Assessment; D012694:Serine; D012907:Smoking
C514392:ARMS2 protein, human; D015415:Biomarkers; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D011506:Proteins; D018799:Intercellular Adhesion Molecule-1; D012694:Serine; D002097:C-Reactive Protein; D000409:Alanine