Original articleAlleles in the HtrA Serine Peptidase 1 Gene Alter the Risk of Neovascular Age-Related Macular Degeneration
Section snippets
Patient Population
The protocol was reviewed and approved by the institutional review boards at the Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, and William Beaumont Hospital, Royal Oak, Michigan, and conforms to the tenets of the Declaration of Helsinki. Eligible patients were enrolled in this study after they gave informed consent in person, over the phone, or through the mail before answering a standardized questionnaire and donating 10 to 50 ml of venous blood. In most cases, the donation of
Results
We identified 23 variants including deletions. Only the SNPs that had a minor allele frequency of ≥5% in the affected and unaffected siblings combined were used for statistical analysis (n = 19) (Table 4 [available at http://aaojournal.org]). Using FBAT, 6 SNPs showed significant association with AMD risk after applying a Bonferroni correction (Table 6 [available at http://aaojournal.org]). Genotype and allele frequencies for each of these SNPs are given in Table 5 (available at //aaojournal.org
Discussion
Two of the 4 novel variants that we identified in HTRA1 have predicted functional effects on the pathophysiology of neovascular AMD. Variant rs2672598 created a binding site for the transcription factor ELK-1, whose activity was reported to be impaired in a patient with a premature form of aging and insulin resistance.27 We hypothesize, then, that if the risk allele of the promoter SNP rs11200638 results in increased expression of HTRA1,12, 13 then the minor allele of rs2672598 might exert a
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Manuscript no. 2007-874.
The authors have no conflict of interest in any materials mentioned in the article.
Supported by grants from the Ruth and Milton Steinbach Fund, New York, New York; Lincy Foundation, Beverly Hills, California; Massachusetts Lions, New Bedford, Massachusetts; Friends of the Massachusetts Eye and Ear Infirmary (MEEI), Boston, Massachusetts; Genetics of Age-Related Macular Degeneration Fund, MEEI, Boston, Massachusetts; Research to Prevent Blindness, New York, New York; Natural Science Foundation of China, Beijing, China (project no. 30730057); and National Institutes of Health, Bethesda, Maryland (nos. EY014458, EY14104, MH44292).