Analysis of the C–Reactive Protein Gene in Patients With Neovascular Age–Related Macular Degeneration

Abstract

Purpose: : The mechanisms that underlie age–related macular degeneration (AMD) are not well understood but increasing evidence indicates that inflammation may play a role. Recently, increased levels of C–Reative Protein (CRP), a marker of inflammation, were shown to increase risk for progression of AMD (Seddon 2005) as well as any type of AMD (Vine et al., 2005), providing support for a role of inflammation in the pathophysiology of AMD. However, a prospective analysis on data from the Cardiovascular Health Study concluded that CRP was not associated with either early or late AMD (neovascular or atrophic) (McGwin et al., 2005). Similarly, a nested case control study from the Beaver Dam Eye Study revealed no association between CRP, early AMD or advanced AMD. Therefore we wanted to examine if the CRP gene was associated with risk of neovascular AMD.

Methods: : We ascertained 154 extremely discordant sibpairs (110 families) where at least one member (the index patient; mean age = 72.4) had neovascular AMD and another member (the unaffected sibling; mean age = 74.3) had normal maculae and was past the age at which the affected sibling was diagnosed with neovascular AMD. Disease status for each participant was confirmed by grading of fundus photographs by at least two of the investigators, or a home visit (n = 6). Leukocyte DNA samples were purified, and 2 fragments of the CRP gene (5’–UTR and both exons) were amplified by PCR and sequenced on an ABI 3100 Genetic Analyzer. All primers were designed to include at least 50bp of sequence outside the exon/intron boundary. All statistical analyses were performed with McNemar’s test.

Results: : The only change that was identified was a Leu184Leu polymorphism. No association with CRP and risk of neovascular AMD was detected (8 informative pairs).

Conclusions: : Our preliminary analysis revealed no associations between CRP genotype and risk of neovascular AMD, although we must caution that the numbers of informative sibpairs was small. Also a variation in the CRP gene, if present, may be located further upstream in the promoter region or possibly in the 3’–UTR region. Therefore, further analysis is ongoing.

Keywords: age-related macular degeneration • gene screening • genetics