The CAPN2/CAPN8 Locus on Chromosome 1q Is Associated with Variation in Serum Alpha-Carotene Concentrations

J Nutrigenet Nutrigenomics. 2016;9(5-6):254-264. doi: 10.1159/000452890. Epub 2016 Dec 22.


Background/aims: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

MeSH terms

  • Adult
  • Amish / genetics
  • Calpain / genetics*
  • Carotenoids / blood*
  • Chromosomes, Human, Pair 1*
  • Diet
  • Female
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Loci*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide


  • CAPN8 protein, human
  • Carotenoids
  • alpha-carotene
  • Calpain
  • CAPN2 protein, human