Conley Yvette P, Jakobsdottir Johanna, Mah Tammy, Weeks Daniel E, Klein Ronald, Kuller Lewis, Ferrell Robert E, Gorin Michael B
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
Hum Mol Genet. 2006 Nov 1;15(21):3206-18. doi: 10.1093/hmg/ddl396. Epub 2006 Sep 25.
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.
年龄相关性黄斑病变（ARM）是老年人群视力损害的一个重要原因。识别该疾病的遗传因素及其与环境暴露的相互作用至关重要。本研究旨在调查使用不同确定方案收集的独立队列中的CFH、ELOVL4、PLEKHA1和LOC387715基因。该研究采用病例对照设计，研究对象最初招募自心血管健康研究（CHS）和年龄相关性眼病研究（AREDS）。在两个队列中，CFH均与ARM显著相关（P≤0.00001）。一项荟萃分析证实，杂合或纯合状态的风险等位基因（OR分别为2.4和6.2；95%CI分别为2.2 - 2.7和5.4 - 7.2）会增加易感性。在两个队列中，LOC387715也与ARM显著相关（P≤0.00001），一项荟萃分析证实，杂合和纯合状态的风险等位基因（OR分别为2.5和7.3；95%CI分别为2.2 - 2.9和5.7 - 9.4）会增加易感性。CFH和LOC387715对ARM风险均显示出等位基因剂量效应，与杂合子相比，任一基因座纯合的个体风险增加两倍以上。与LOC387715紧密连锁的PLEKHA1在AREDS队列中与ARM状态显著相关，但在CHS队列中不相关，且在两个队列中ELOVL4与ARM均无显著相关性。在两个队列中，CFH和LOC387715的联合作用最好用独立相乘效应来描述，且无显著相互作用。在两个队列中，这两个基因与吸烟的相互作用均不显著。本研究通过评估关于ARM状态有不同确定方案的队列并进行荟萃分析，为CFH和LOC387715基因在ARM易感性方面提供了额外支持。
