To investigate association of scavenger receptor class B, member 1
(SCARB1) genetic variants with serum carotenoid levels
of lutein (L) and zeaxanthin (Z) and macular pigment optical density
A cross-sectional study of healthy adults aged 20-70.
302 participants recruited following local advertisement.
MPOD was measured by customized heterochromatic flicker photometry.
Fasting blood samples were taken for serum L and Z measurement by HPLC and
lipoprotein analysis by spectrophotometric assay. Forty-seven single
nucleotide polymorphisms (SNPs) across SCARB1 were
genotyped using Sequenom technology. Association analyses were performed
using PLINK to compare allele and haplotype means, with adjustment for
potential confounding and correction for multiple comparisons by permutation
testing. Replication analysis was performed in the TwinsUK and CAREDS
Main outcome measures
Odds ratios (ORs) for macular pigment optical density area, serum
lutein and zeaxanthin concentrations associated with genetic variations in
SCARB1 and interactions between SCARB1
Following multiple regression analysis with adjustment for age, body
mass index, sex, high-density lipoprotein cholesterol (HDLc), low-density
lipoprotein cholesterol (LDLc), triglycerides, smoking, dietary L and Z
levels, 5 SNPs were significantly associated with serum L concentration and
1 SNP with MPOD (P<0.01). Only the association between rs11057841 and
serum L withstood correction for multiple comparisons by permutation testing
(P<0.01) and replicated in the TwinsUK cohort (P=0.014). Independent
replication was also observed in the CAREDS cohort with rs10846744
(P=2×10−4), a SNP in high linkage
disequilibrium with rs11057841 (r2=0.93). No significant
interactions by sex were found. Haplotype analysis revealed no stronger
association than obtained with single SNP analyses.
Our study has identified association between rs11057841 and serum L
concentration (24% increase per T allele) in healthy subjects, independent
of potential confounding factors. Our data supports further evaluation of
the role for SCARB1 in the transport of macular pigment and
the possible modulation of AMD risk through combating the effects of
oxidative stress within the retina.