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The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples.

ABSTRACT: PURPOSE:Age-related macular degeneration (AMD) is a multifactorial blinding disease in the elderly. LOC387715 harbors a single-nucleotide polymorphism that has an association with AMD. This study was conducted to confirm the association between LOC387715 and AMD and to refine estimates of the impact of this gene variation in using samples from three studies: an Australian population-based study and two U.S. clinic-based case-control studies. METHODS:Cases and controls were collected from a National Eye Institute (NEI) clinical protocol (n = 240), the Age-Related Eye Disease Study (AREDS; n = 488), and the Blue Mountains Eye Study (BMES; n = 851). After DNA extraction, subjects were genotyped for the LOC387715 Ala69Ser polymorphism (rs10490924). RESULTS:The combined NEI and AREDS samples yielded odds ratios (ORs) of 2.61 (95% CI 1.89-3.61, P = 1.42 x 10(-9)) and 8.59 (95% CI 4.49-16.5, P = 3.56 x 10(-13)) for the heterozygous and homozygous risk alleles, respectively. The corresponding odds ratios in the BMES sample were 1.69 (95% CI: 1.25-2.28, P = 0.0007) and 2.20 (95% CI: 1.05-4.62, P = 0.038) for the heterozygous and homozygous groups. Neither set of samples showed statistically significant interaction with smoking, although there appeared to be a trend of interaction between smoking and LOC387715 for risk of advanced AMD. CONCLUSIONS:Although these data from three case-control samples support an AMD genetic risk marker harbored within LOC387715, the nested case-control data from the population-based BMES samples showed lower estimates than from the clinic-based samples. This may be because the BMES samples consisted of largely early AMD cases while the clinic-based AMD samples consisted exclusively of advanced cases.

SUBMITTER: Ross RJ

PROVIDER: S-EPMC1885234 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples.

Ross Robert J RJ Bojanowski Christine M CM Wang Jie Jin JJ Chew Emily Y EY Rochtchina Elena E Ferris Frederick L FL Mitchell Paul P Chan Chi-Chao CC Tuo Jingsheng J

Investigative ophthalmology & visual science 20070301 3

<h4>Purpose</h4>Age-related macular degeneration (AMD) is a multifactorial blinding disease in the elderly. LOC387715 harbors a single-nucleotide polymorphism that has an association with AMD. This study was conducted to confirm the association between LOC387715 and AMD and to refine estimates of the impact of this gene variation in using samples from three studies: an Australian population-based study and two U.S. clinic-based case-control studies.<h4>Methods</h4>Cases and controls were collect ...[more]

PMID: 17325155

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Project description:BACKGROUND: Age-related macular degeneration (AMD) is the major cause of blindness in the elderly. Those with the neovascular end-stage of disease have irreversible loss of central vision. AMD is a complex disorder in which genetic and environmental factors play a role. Polymorphisms in the complement factor H (CFH) gene, LOC387715, and the HTRA1 promoter are strongly associated with AMD. Smoking also contributes to the etiology. We aimed to provide a model of disease risk based on these factors. METHODS AND FINDINGS: We genotyped polymorphisms in CFH and LOC387715/HTRA1 in a case-control study of 401 patients with neovascular AMD and 266 controls without signs of disease, and used the data to produce genetic risk scores for the European-descent population based on haplotypes at these loci and smoking history. CFH and LOC387715/HTRA1 haplotypes and smoking status exerted large effects on AMD susceptibility, enabling risk scores to be generated with appropriate weighting of these three factors. Five common haplotypes of CFH conferred a range of odds ratios (ORs) per copy from 1 to 4.17. Most of the effect of LOC387715/HTRA1 was mediated through one detrimental haplotype (carriage of one copy: OR 2.83; 95% confidence interval [CI] 1.91-4.20), with homozygotes being at particularly high risk (OR 32.83; 95% CI 12.53-86.07). Patients with neovascular macular degeneration had considerably higher scores than those without disease, and risk of blinding AMD rose to 15.5% in the tenth of the population with highest predicted risk. CONCLUSIONS: An individual's risk of developing AMD in old age can be predicted by combining haplotype data with smoking status. Until there is effective treatment for AMD, encouragement to avoid smoking in those at high genetic risk may be the best option. We estimate that total absence of smoking would have reduced the prevalence of severe AMD by 33%. Unless smoking habits change or preventative treatment becomes available, the prevalence of AMD will rise as a consequence of the increasing longevity of the population.

Dataset Information

The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples.

Publications

The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples.

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