title: The CAPN2/CAPN8 Locus on Chromosome 1q Is Associated with Variation in Serum Alpha-Carotene Concentrations.
abstract: Alpha-carotene is a provitamin A carotenoid present in fruits and vegetables. Higher serum concentrations of α-carotene have been associated with lower risk of cancer and all-cause mortality. Previous studies have suggested that genetic variants influence serum concentrations of provitamin A carotenoids, but to date no variants have been robustly associated with serum α-carotene concentrations. The aim of this study was to identify genetic associations with serum α-carotene concentrations using the genome-wide association study (GWAS) approach.
  
  
  
  A GWAS of serum α-carotene concentrations was conducted in 433 Old Order Amish adults who had consumed a 6-day controlled diet. Linear regression models adjusting for age, gender, and family structure were utilized to evaluate associations between genetic variants and serum α-carotene concentrations.
  
  
  
  Genome-wide significant associations with α-carotene concentrations were observed for loci on chromosome 1q41 between the genes CAPN2 and CAPN8 (rs12137025, p = 3.55 × 10-8), chromosome 2p21 in PRKCE (rs2594495, p = 1.01 × 10-8), and chromosome 4q34 (rs17830069, p = 2.89 × 10-8).
  
  
  
  We identified 3 novel loci associated with serum α-carotene concentrations among a population that consumed a controlled diet. While replication is necessary, the CAPN2/CAPN8 locus provides compelling evidence for an association with serum α-carotene concentrations and may suggest a relationship with the development and progression of cancers.
authors.affiliation: Department of Family &amp; Community Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: D'Adamo
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Dawson
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges-Armstrong
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.forename: Nanette I
authors.initials: NI
authors.lastname: Steinle
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McArdle
mesh_terms: D000328:Adult; D061365:Amish / Q000235:genetics; D002154:Calpain / Q000235:genetics*; D002338:Carotenoids / Q000097:blood*; D002878:Chromosomes, Human, Pair 1; D004032:Diet; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C000624551:CAPN8 protein, human; D002338:Carotenoids; C041635:alpha-carotene; D002154:Calpain; C569870:CAPN2 protein, human