Genetic variants in BCMO1 and CD36 are associated with plasma lutein concentrations and macular pigment optical density in humans.

Unlabelled: Lutein is recovered at high concentration in the human macula lutea. Recent studies suggest that this micronutrient might be implicated in prevention of age-related macular degeneration.

Objective: to identify genes which affect blood and retina lutein concentrations among candidate genes (intestinal sterol transporters and carotenoid oxygenases).

Design: a comparative plus an observational study.

Participants: twenty-nine healthy subjects for the comparative study and 622 subjects for the observational study.

Intervention And Methods: all the participants were genotyped for single nucleotide polymorphisms (SNPs) in the candidate genes. Fasting plasma lutein concentrations were measured in all the participants and after 6 months' supplementation, with either a lutein-rich supplement or a placebo, in the 29 subjects who participated in the comparative study. Macular pigment optical density (MPOD), which is a measure of macula concentration of lutein, was measured before and after the dietary intervention in the 29 subjects. Associations between SNPs and plasma lutein and MPOD were assessed by partial least square (PLS) regression followed by univariate analysis. Observed associations between SNPs and plasma lutein were verified by haplotype-based association analysis in the cohort of 622 subjects.

Main Outcome Measures: plasma lutein levels and MPOD.

Results: six SNPs in four genes (ABCG8, BCMO1, CD36, and NPC1L1) explained 25% and 38% of the plasma and MPOD variance, respectively. Subjects with TT at the BCMO1 rs7501331 locus had lower (P < 0.05) plasma lutein than CT subjects. Subjects with CC at the CD36 rs13230419 locus had lower (P < 0.05) plasma lutein than subjects who carried a T allele. The association between CD36 and plasma lutein was confirmed in the cohort of 622 subjects. Subjects with TT at the BCMO1 rs7501331 locus had a higher (P < 0.05) MPOD, and subjects with GG at rs1761667 CD36 locus had a higher (P < 0.05) MPOD than those with an A allele.

Conclusions: these results suggest that BCMO1 and CD36 are implicated in plasma and retina concentrations of lutein and that genetic variants in these genes can modulate blood and retina concentrations of lutein.