Identification of Genetic Polymorphisms Associated with Interindividual Variability of Vitamin A Concentration in Adipose Tissue of Healthy Male Adults.

Abstract

Background: Adipose tissue vitamin A (VA), that is, mainly retinol (RET) and its esters, comes from preformed VA and proVA carotenoids present in our food. Adipose tissue VA acts as hormonal cue maintaining essential aspects of adipocyte biology, which includes fat mobilization and catabolism, energy balance, and glucose homeostasis, and it is thus of particular interest to study its determinants, including genetic ones.

Objectives: This study aimed to identify genetic variations associated with adipose tissue VA concentration.

Methods: Forty-two healthy male adults received, in a randomized crossover design, 3 test meals. Periumbilical adipose tissue samples were collected on 6 occasions, that is, at fast and 8 h after consumption of each meal. RET concentration was measured in both plasma and the adipose tissue following saponification. Participants were genotyped using whole-genome microarrays. A total of 1305 single nucleotide polymorphism (SNPs) in or near 27 candidate genes were included for univariate analysis. Partial least squares (PLS) regression was carried out to find the best combination of SNPs associated with the interindividual variability in adipose tissue RET concentration.

Results: Adipose tissue RET concentration was not associated with plasma RET concentrations (r = -0.184, P = 0.28). Interindividual variability of adipose tissue RET concentration was high (CV = 62%). Twenty-nine SNPs were significantly (P < 0.05) associated with adipose tissue RET concentration and a PLS regression model identified 16 SNPs as explanatory variables of this concentration. The SNPs were in or near peroxisome proliferator activated receptor gamma, retinoid X receptor alpha, signaling receptor and transporter of retinol, cluster of differentiation 36, free fatty acid receptor 4, aldehyde dehydrogenase 1 family member A1, monoglyceride lipase, DGAT2, and polycystic kidney disease 1-like 2.

Conclusions: A combination of 16 SNPs has been associated with the interindividual of adipose tissue VA concentration in humans. This trial was registered at clinicaltrials.gov as NCT02100774.