《美国医学协会杂志》4月24日发表的研究报告说，美国科学家已经确认了两种导致老年性黄斑变性的特殊基因。研究发现，老年性黄斑变性病情恶化与两种特殊基因——CFHY402H和LOC387715A69S的变异有关。老年性黄斑变性是发生于中老年眼底黄斑部的一种退行病变。这种疾病是西方发达国家50岁以上人群致盲的首要原因。
原始出处:
Journal of American Medical Association，JAMA
Vol. 297 No. 16, April 25, 2007
Association of CFH Y402H and LOC387715 A69S With Progression of Age-Related Macular Degeneration
Johanna M. Seddon, MD, ScM; Peter J. Francis, MD, PhD; Sarah George, MPH; Dennis W. Schultz, PhD; Bernard Rosner, PhD; Michael L. Klein, MD
JAMA. 2007;297:1793-1800.
Context Studies have reported that single-nucleotide polymorphisms in the genes CFH and LOC387715 are associated with age-related macular degeneration (AMD).
Objective To assess whether these genetic variants have prognostic importance for progression to advanced AMD and related visual loss.
Design, Setting, and Participants Prospective analysis of 1466 white participants in the Age-Related Eye Disease Study (AREDS), a US multicenter clinical trial conducted from 1990 to 2001 with a mean follow-up time of 6.3 years. Age-related macular degeneration status was determined by grading of fundus photographs. Progression (n = 281) was defined as newly diagnosed advanced AMD (geographic atrophy, exudative disease, or AMD causing visual loss) in one or both eyes during the course of the study. Genotypic analysis was conducted in 2006.
Main Outcome Measure Incidence rates of dry and neovascular advanced AMD.
Results The CFH Y402H and LOC387115 A69S polymorphisms were each independently related to progression from early or intermediate stages to advanced stages of AMD, controlling for demographic factors, smoking, body mass index, and AREDS vitamin-mineral treatment assignment, with odds ratios (ORs) of 2.6 (95% confidence interval [CI], 1.7-3.9) for CFH and 4.1 (95% CI, 2.7-6.3) for LOC387715 for the homozygous risk genotypes (P<.001 for trend for each additional risk allele for both genes). The effect of LOC387715 was stronger for progression to neovascular disease (OR, 6.1; 95% CI, 3.3-11.2) compared with geographic atrophy (OR, 3.0; 95% CI, 1.4-6.5) relative to no progression for the homozygous risk state. The presence of all adverse factors (both risk genotypes, smoking, and body mass index 25) increased risk 19-fold. Smoking and high body mass index increased odds of progression within each risk genotype. Genetic plus nongenetic risk scores provided an area under the receiver operating characteristic curve of up to 0.78.
Conclusions Common polymorphisms in the genes CFH and LOC387715 are independently related to AMD progression after adjustment for other known AMD risk factors. Presence of these polymorphisms plus AREDS vitamin-mineral treatment, smoking, and body mass index of 25 or higher identify patients who are highly susceptible to developing advanced stages of this visually disabling disease.
Author Affiliations: Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology, Tufts-New England Medical Center (Dr Seddon), Departments of Epidemiology (Dr Seddon) and Biostatistics (Dr Rosner), Harvard School of Public Health, Harvard Graduate School of Education (Ms George); and Channing Laboratory, Harvard Medical School (Dr Rosner), Boston; and Macular Degeneration Center, Casey Eye Institute, Oregon Health and Science University, Portland (Drs Francis, Schultz, and Klein).
