Adipose tissue cadmium concentrations as potential determinants of serum PON1 status in an adult cohort from Southern Spain

Paraoxonase 1 (PON1) is an antiatherogenic enzyme inhibited by environmental stressors such as cadmium (Cd). Thus, this human study aimed to assess (1) the associations between adipose tissue Cd concentrations and serum PON1 status and (2) the influence of the PON1_Q192R phenotype on the susceptibility of PON1 status to Cd. As a continuation from previous work, a subsample from the GraMo cohort (Granada, Spain) was studied. Three PON1 activities using non-organophosphorous substrates {PALS (phenyl acetate in the absence of NaCl), PAHS (phenyl acetate in 2 M NaCl) and CMPA [4-(chloromethyl)phenyl acetate]} were assayed in serum (n = 296) to obtain the three functional PON1_Q192R phenotypes (QQ, QR and RR). Complementarily, Cd concentrations in adipose tissue (n = 226) and information on socio-demographic characteristics, lifestyle, diet and health status acquired by face-to-face interviews were available. The associations between PON1 activities in serum and Cd concentrations in adipose tissue (subset of n = 138) were explored by using linear regression models, which were adjusted for sex, alcohol consumption and PON1_Q192R phenotype. Additionally, benchmark dose (BMD) modelling was performed. Higher adipose tissue Cd concentrations were associated with lower PON1 activities. PON1_Q192R specific susceptibility to Cd increased in the order QQ < QR < RR. The Cd BMD ranges for an averaged subject were 0.002-0.016 and 0.046-0.115 mg_Cd/kg_{adipose-tissue} for RR and QR, respectively. For QQ cases, the BMD were higher than the Cd concentrations found in adipose tissue. These results suggest that part of the increased susceptibility of the RR cases to cardiovascular diseases might putatively be mediated by its higher sensitivity to Cd, with adipose tissue Cd levels serving as a biomarker of chronic exposure.