LIPC and LPL polymorphisms, age-related macular degeneration and plasma lutein and zeaxanthin: the Alienor Study

Abstract

Purpose: Genes implicated in high density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). HDL, transport the two carotenoids, lutein (L) and zeaxanthin (Z), which are highly suspected to play a key-role in the protection against AMD. We aimed at assessing associations of some genes implicated in HDL metabolism with AMD and plasma L and Z

Methods: The Alienor study is a prospective population-based study on nutrition and age-related eye diseases, performed in 963 residents of Bordeaux, aged 73 years or more (2006-08). Early and late AMD were graded according to the international classification, from non mydriatic colour retinal photographs. Plasma L and Z were determined by normal-phase high-performance liquid chromatography. A genome-wide scan was performed. Genotypes data for rs10468017 (LIPC), rs3764261 (CETP) and rs12678919 (LPL) were available. Genotypes for rs10490924 (ARMS2/HTRA1), rs493258 (LIPC), rs9621532 and rs1883025 (ABCA1) SNPs were imputed using Markov Chain-based haplotyper (MACH v1.0.16a) software and the 1000 Genomes Project data. Persons implicated in AMD classification had no access to either plasma or genetic data. Associations of late AMD with genetic polymorphisms were estimated using Generalized Estimating Equation logistic regressions. Associations of L and Z with genetic polymorphisms were estimated using linear regression

Results: After multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk of 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 Z concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Associations of AMD with LIPC rs10468017 were weaker, and did not reach statistical significance after full multivariate adjustment (early AMD, OR=0.73, 95%CI: 0.41-1.29; p=0.20 and late AMD, OR=0.21, 95%CI: 0.03-1.61; p=0.13). 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 L (p=0.047). Associations between CETP and ABCA1 polymorphisms and AMD did not reach statistical significance

Conclusions: These findings suggest that LIPC and LPL genes, implicated in HDL metabolism, could both modify the risk for AMD and the metabolism of L and Z

Keywords: 412 age-related macular degeneration • 539 genetics • 464 clinical (human) or epidemiologic studies: risk factor assessment