The HtrA1 promoter polymorphism, smoking, and age-related macular degeneration in multiple case-control samples.
OBJECTIVE
To assess the association and combined effect on the risk of age-related macular degeneration (AMD) by the HtrA1 and complement factor H (CFH) polymorphisms, smoking, and serum cholesterol.


METHODS
Clinic-based and population-based case control study.


METHODS
A total of 805 AMD cases and 921 controls from The Eye Clinic of National Eye Institute, Age-Related Eye Diseases Study, Blue Mountain Eye Study Cohort, and Minnesota Lions Eye Bank.


METHODS
DNA samples were genotyped for polymorphisms of rs11200638 in HtrA1 promoter and rs380390 in CFH. HtrA1 protein in ocular tissue was measured. Interactions of the HtrA1 risk allele with the CFH risk variant, smoking status, and cholesterol were assessed.


METHODS
AMD was evaluated by retinal specialists, and AMD subtypes (geographic atrophy and neovascularization) were determined.


RESULTS
Strong associations of the HtrA1 risk allele (A) with AMD were present in all sample sets. A similar magnitude of association was observed for central geographic atrophy and neovascular AMD. The combination of the HtrA1 and CFH risk alleles increased AMD susceptibility, as did the combination of the HtrA1 risk allele with smoking. No combined effect of HtrA1 risk allele and cholesterol level was found. Enhanced expression of HtrA1 protein was detected in retina with AMD.


CONCLUSIONS
Findings from multiple samples support an AMD genetic variant harbored within HtrA1. The risk of advanced AMD increased when the presence of risk alleles from HtrA1 was combined with either CFH risk alleles or history of smoking.
Tuo
Jingsheng
J
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
Ross
Robert J
RJ
Reed
George F
GF
Yan
Qing
Q
Wang
Jie Jin
JJ
Bojanowski
Christine M
CM
Chew
Emily Y
EY
Feng
Xiao
X
Olsen
Timothy W
TW
Ferris
Frederick L
FL
Mitchell
Paul
P
Chan
Chi-Chao
CC
D000368:Aged; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007124:Immunoenzyme Techniques; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000235:genetics*
C493495:CFH protein, human; D017242:Complement Factor H; D002784:Cholesterol; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases