Single Nucleotide Polymorphisms in CD36 Are Associated with Macular Pigment among Children

Abstract

Background: High macular pigment optical density (MPOD) has been associated with improved eye health and better cognitive functions. Genetic variations have been associated with MPOD in adults. However, these associations between genetic variations and MPOD have not been studied in children.

Objectives: This was a secondary analysis of the FK2 (Fitness Improves Thinking in Kids 2) trial (n = 134, 41% male). The aim was to determine differences in MPOD among children (aged 7-9 y) based on genetic variants that either are biologically relevant to lutein (L) and zeaxanthin (Z) accumulation or have been associated with MPOD in adults.

Methods: MPOD was measured using customized heterochromatic flicker photometry via a macular densitometer. DXA was used to assess whole-body and visceral adiposity. DNA was extracted from saliva samples and was genotyped for 26 hypothesis-driven single nucleotide polymorphisms and 75 ancestry-informative markers (AIMs). Habitual diet history was obtained via 3-d food logs completed by parents (n = 88). General linear models were used to compare MPOD between different genotypes. Principal component analysis was performed for the AIMs to account for ethnic heterogeneity.

Results: Children carrying ≥1 minor allele on β-carotene-15,15'-monooxygenase (BCO1)-rs7501331 (T allele) (P = 0.045), cluster of differentiation 36(CD36)-rs1527483 (T allele) (P = 0.038), or CD36-rs3173798 (C allele) (P = 0.001) had significantly lower MPOD (range: 14.1%-26.4%) than those who were homozygotes for the major alleles. MPOD differences based on CD36-rs3173798 genotypes persisted after adjustment for dietary L and Z intake.

Conclusions: The findings indicate that genetic variations of CD36 and BCO1 contribute to MPOD in children. The influence of genetic variation in CD36-rs3173798 persisted after adjusting for variation in dietary intake.This trial was registered at clinicaltrials.gov as NCT01619826.

Keywords: carotenoids; lutein; macular pigment optical density; nutrigenetics; pediatric; zeaxanthin.

FIGURE 1

MPOD among Fitness Improves Thinking in Kids 2 trial participants at age 7–9 y with BCO1-rs7501331 CT + TT genotypes (n = 48) or CC genotype (n = 82) (A), CD36-rs1527483 CT + TT genotypes (n = 21) or CC genotype (n = 109) (B), and CD36-rs3173798 CT + CC genotypes (n = 34) or TT genotype (n = 52) (C). MPOD differences were determined through general linear models adjusted for ancestry, age, sex, and visceral fat mass for BCO1-rs7501331 and CD36-rs3173798. General linear models for CD36-rs3173798 were further adjusted for dietary lutein and zeaxanthin intake. Values are means ± SEs. *,**Different from corresponding homozygote: *P < 0.05, **P < 0.01. BCO1, β-carotene-15,15′-monooxygenase; MPOD, macular pigment optical density.