CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses

Yvette P. Conley, Johanna Jakobsdottir, Tammy Mah, Daniel E. Weeks, Ronald Klein, Lewis Kuller, Robert E. Ferrell, Michael B. Gorin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3206-3218
Number of pages13
JournalHuman Molecular Genetics
Volume15
Issue number21
DOIs
Publication statusPublished - 1 Nov 2006

Bibliographical note

Funding Information:
We want to especially acknowledge the AREDS participants and the AREDS Research Group as well as the CHS participants and CHS investigators for their valuable contribution to this research. Regarding the meta-analyses, we are also grateful to Dr Swaroop and colleagues for providing CFH genotype count data, and Dr Schmidt and colleagues for providing LOC387715 genotype count data. This study was supported by NEI grant R01EY009859, The Steinbach Foundation, New York, Research to Prevent Blindness, New York and the Eye and Ear Foundation of Pittsburgh (all to M.B. Gorin). The CHS-related research reported in this article was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222 and U01 HL080295 from the National Heart, Lung and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of participating CHS investigators and institutions can be found at http://www.chs-nhlbi.org.

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