Genetic Determinants of Interindividual Differences in Provitamin A Carotenoid Concentrations in Human Adipose Tissue

Adipose tissue is a major storage site for provitamin A carotenoids (proVA CAR)-mainly β-carotene (BCAR), α-carotene (ACAR), and β-cryptoxanthin (BCRY). However, the determinants of their concentrations in this tissue remain poorly understood. This study aimed to identify genetic variants associated with adipose tissue proVA CAR concentrations. Periumbilical adipose tissue samples were collected on six occasions in 43 healthy adult males and proVA CAR concentrations were quantified by HPLC. Participants were genotyped for 2,398 SNPs in 44 candidate genes involved in CAR and lipid metabolism, and genetic associations were assessed using partial least squares (PLS) regression. Adipose tissue proVA CAR concentrations ranked as BCAR > ACAR > BCRY, with CV ranging from 54 to 66%. PLS regression models integrating fasting plasma proVA CAR concentrations and SNPs explained 69, 59, and 67% of the variability in BCAR, ACAR, and BCRY concentrations, respectively. In a multivariate PLS regression model, the main determinants of proVA CAR concentrations were fasting plasma BCAR and ACAR concentrations and four SNPs-rs4694627 (CXCL8), rs7558381 (IRS1), rs709157 and rs1152004 (PPARG). Interindividual variability in adipose tissue proVA CAR concentrations is partly explained by genetic variation in genes involved in CAR and lipid metabolism. Clinical Trial Registry: ClinicalTrials.gov registration number NCT02100774.