title: Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids.
abstract: OBJECTIVE
  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 (MPOD).
  
  
  METHODS
  A cross-sectional study of healthy adults aged 20 to 70.
  
  
  METHODS
  We recruited 302 participants after local advertisement.
  
  
  METHODS
  We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography 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 Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts.
  
  
  METHODS
  Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender.
  
  
  RESULTS
  After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and 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)), an SNP in high linkage disequilibrium with rs11057841 (r(2) = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses.
  
  
  CONCLUSIONS
  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 age-related macular degeneration risk through combating the effects of oxidative stress within the retina.
  
  
  BACKGROUND
  Proprietary or commercial disclosures may be found after the references.
authors.affiliation: Centre for Public Health, Royal Victoria Hospital, Queen's University Belfast, Belfast, Northern Ireland. g.j.mckay@qub.ac.uk
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: McKay
authors.forename: Edward
authors.initials: E
authors.lastname: Loane
authors.forename: John M
authors.initials: JM
authors.lastname: Nolan
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Patterson
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Meyers
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mares
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Yonova-Doing
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
authors.forename: Stephen
authors.initials: S
authors.lastname: Beatty
authors.forename: Giuliana
authors.initials: G
authors.lastname: Silvestri
mesh_terms: D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation; D060005:Genotyping Techniques; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D014975:Lutein / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010783:Photometry; D020641:Polymorphism, Single Nucleotide; D012160:Retina / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics*; D014792:Visual Acuity; D024341:Xanthophylls / Q000097:blood* / Q000235:genetics; D055815:Young Adult; D065146:Zeaxanthins
chemical_list: D008074:Lipoproteins; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D024341:Xanthophylls; D065146:Zeaxanthins; D014975:Lutein
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