title: CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses.
abstract: 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 (P</=0.00001) 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.
authors.affiliation: Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, The Eye and Ear Institute Building, 203 Lothrop Street, Pittsburgh, PA 15261, USA
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.forename: Johanna
authors.initials: J
authors.lastname: Jakobsdottir
authors.forename: Tammy
authors.initials: T
authors.lastname: Mah
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Lewis
authors.initials: L
authors.lastname: Kuller
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Michael B
authors.initials: MB
authors.lastname: Gorin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; C418975:ELOVL4 protein, human; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C435927:PLEKHA1 protein, human; D011506:Proteins; D017242:Complement Factor H