Abstract
BackgroundSeveral genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations.MethodsAlienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high-performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC), rs3764261 (CETP), rs12678919 (LPL) and rs1883025 (ABCA1).ResultsAfter multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively), and with higher plasma zeaxanthin concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45-1.00; p=0.05) and both with plasma lipids and plasma lutein (p=0.047). Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance.ConclusionThese findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin.
Highlights
Age-related macular degeneration (AMD) is a degenerative disease of the central part of the retina, responsible for half of the cases of blindness in industrialized countries [1]
Mean of age was 80.2 years (± 4.4), 62.0 % of the sample were women and 32.8 % declared lipid lowering medication use. 64.6 % had never smoked, 18.2 % had smoked less than 20 pack-years and 17.2 % more than 20 pack-years
The CT genotype of LIPC rs10468017 SNP was significantly associated with a decreased risk for early age-related macular degeneration (AMD) in model 1
Summary
Age-related macular degeneration (AMD) is a degenerative disease of the central part of the retina (macula), responsible for half of the cases of blindness in industrialized countries [1] This disease affects 2.5 million subjects in Europe [2] and 1.75 million in the USA [3]. It comprises two late forms both associated with severe visual impairment (neovascular and atrophic AMD), generally preceded by early, asymptomatic, retinal abnormalities (drusen, pigmentary abnormalities). It is a multifactorial disorder involving genetic and environmental factors [4]. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations
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