DISTRIBUTION OF APOE ALLELES AMONG PATIENTS WITH NEOVASCULAR AGE–RELATED MACULAR DEGENERATION AND THEIR UNAFFECTED SIBLINGS

Abstract

Abstract: : Purpose: To examine the distribution of the E2, E3, and E4 alleles of the apolipoprotein E (APOE) gene among siblings with and without neovascular age–related macular degeneration (AMD) making up extremely discordant sibpairs. Methods: We ascertained 44 sibships in which at least one member has the neovascular form of AMD in at least one eye and at least one sibling has normal maculae and is past the age at which the affected sibling was diagnosed with neovascular AMD. We selected the affected index patient (mean age = 74.0 years, SD = 7.0) from each of these sibships and randomly selected one eligible unaffected sibling (mean age = 77.3 years, SD = 7.5) from each sibship. Disease status is confirmed by fundus photographs of every participant by at least two of the investigators except in 4 cases where a home visit was conducted by one of the investigators. Leukocyte DNA samples were purified, and exon 4 of the APOE gene was amplified by PCR. APOE genotypes were determined through agarose gel electrophoresis of DNA fragments resulting from Hha1 digestion and/or through direct sequencing. Results: The E4 allele was found heterozygously or homozygously in both siblings of 7 pairs, in the affected sibling but not the unaffected sibling in 1 pair, in the unaffected sibling but not the affected sibling in 9 pairs, and in neither sibling in 27 pairs. This distribution is different from what would be expected with a random distribution of e4 alleles among the siblings (p = 0.03, using the McNemar’s test). No statistically significant association was found with the E2 allele, since one pair had this allele heterozygously or homozygously in both members, 3 had the allele in the affected member but not the unaffected member, 1 had the allele in the unaffected member but not the affected member, and 39 had it in neither member (p = 0.6). Conclusions: .The more frequent occurrence of the E4 allele in unaffected siblings compared to affected siblings is in accord with previous reports (which did not use the discordant sibpair approach) that suggested that this allele could be associated with a reduced risk for neovascular AMD

Keywords: age–related macular degeneration • choroid: neovascularization • genetics