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

Christopher R. D'Adamo, Valerie J. Dawson, Kathleen A. Ryan, Laura M. Yerges-Armstrong, Richard D. Semba, Nanette I. Steinle, Braxton D. Mitchell, Alan R. Shuldiner, Patrick F. McArdle

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)254-264
Number of pages11
JournalJournal of Nutrigenetics and Nutrigenomics
Issue number5-6
StatePublished - Apr 1 2017


  • Alpha-carotene
  • CAPN2
  • CAPN8
  • Carotenoids
  • Genome-wide association study
  • Old Order Amish

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science
  • Genetics


Dive into the research topics of 'The CAPN2/CAPN8 Locus on Chromosome 1q Is Associated with Variation in Serum Alpha-Carotene Concentrations'. Together they form a unique fingerprint.

Cite this