Human Molecular Genetics Advance Access originally published online on September 25, 2006
Human Molecular Genetics 2006 15(21):3206-3218; doi:10.1093/hmg/ddl396
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CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses
1 Department of Health Promotion and Development, School of Nursing, 2 Department of Human Genetics, Graduate School of Public Health, 3 Department of Biostatistics, Graduate School of Public Health, 4 Department of Ophthalmology, School of Medicine and 5 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, The Eye and Ear Institute Building, 203 Lothrop Street, Pittsburgh, PA 15261, USA and 6 Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA
* To whom correspondence should be addressed. Tel: +1 4126477726; Fax: +1 4126475880; Email: gorinmb{at}upmc.edu
Received August 9, 2006; Accepted September 15, 2006
Age-related maculopathy (ARM) is an important cause of visual impairment in the elderly population. It is of crucial importance to identify genetic factors and their interactions with environmental exposures for this disorder. This study was aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in independent cohorts collected using different ascertainment schemes. The study used a case–control design with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). CFH was significantly associated with ARM in both cohorts (P
0.00001). A meta-analysis confirmed that the risk allele in the heterozygous or homozygous state (OR, 2.4 and 6.2; 95% CI, 2.2–2.7 and 5.4–7.2, respectively) confers susceptibility. LOC387715 was also significantly associated with ARM in both cohorts (P0.00001) and a meta-analysis confirmed that the risk allele in the heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2–2.9 and 5.7–9.4, respectively) confers susceptibility. Both CFH and LOC387715 showed an allele-dose effect on the ARM risk, individuals homozygous at either locus were at more than two-fold risk compared to those heterozygous. PLEKHA1, which is closely linked to LOC387715, was significantly associated with ARM status in the AREDS cohort, but not the CHS cohort and ELOVL4 was not significantly associated with ARM in either cohort. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. This study provides additional support for the CFH and LOC387715 genes in ARM susceptibility via the evaluation of cohorts that had different ascertainment schemes regarding ARM status and through the meta-analyses.
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