HTRA1 promoter polymorphism and risk of age-related macular degeneration: a meta-analysis.
OBJECTIVE
To clarify the role of human high-temperature requirement A-1 (HTRA1) gene promoter polymorphism (-512G>A) in age-related macular degeneration (AMD).


METHODS
Relevant studies were identified by searching PubMed and EMBASE database. A logistic regression analysis proposed for molecular association studies was carried out to estimate the genetic effect and the possible genetic model of action.


RESULTS
Fourteen case-control studies were included in this meta-analysis. There was strong evidence for an association between HTRA1 -512G>A polymorphism and AMD (p < 0.001). The genetic model test indicated that the genetic model was most likely to be co-dominant. Overall, our meta-analysis showed that AA and GA genotypes were associated with increased risk of AMD (AA vs. GG: odds ratio(1) [OR(1)] = 7.46; 95% confidence interval [CI] = 6.16-9.04; GA vs. GG: OR(2) = 2.27, 95% CI = 2.02-2.55). In stratified analysis by ethnicity and age, the genetic effect seemed to be stronger in Caucasians and subjects > or =73 years of age than in Asians and subjects <73 years of age. When subgroup analysis was conducted by AMD type, significant association was noted for wet AMD but not for dry AMD.


CONCLUSIONS
This meta-analysis summarizes the strong evidence for an association between HTRA1 -512G>A polymorphism and AMD and indicates a co-dominant model of action.
National Shanghai Center for New Drug Safety Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, China. naping.tang@gmail.com
Na-Ping
NP
Tang
Bo
B
Zhou
Bin
B
Wang
Rong-Bin
RB
Yu
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*
D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases