Association between C-reactive protein and adiposity in women.

Abstract

The link between C-reactive protein (CRP) and adiposity deserves to be further explored, considering the controversial diabetogenic role of CRP. We explored the potential causal role of CRP on measures of adiposity. We used a Mendelian randomization approach with the CRP and LEPR genes as instrumental variables in a cross-sectional Caucasian population-based study comprising 2526 men and 2836 women. Adiposity was measured using body mass index (BMI), fat and lean mass estimated by bioelectrical impedance, and waist circumference. Log-transformed CRP explained by the rs7553007 single-nucleotide polymorphism tagging the CRP gene was significantly associated with BMI [regression coefficient: 1.22 (0.18; 2.25), P = 0.02] and fat mass [2.67 (0.65; 4.68), P = 0.01] but not with lean mass in women, whereas no association was found in men. Log-transformed CRP explained by the rs1805096 LEPR single-nucleotide polymorphism was also positively associated, although not significantly, with BMI or fat mass. The combined CRP-LEPR instrument explained 2.24 and 0.77% of CRP variance in women and men, respectively. Log-transformed CRP explained by this combined instrument was significantly associated with BMI [0.98 (0.32; 1.63), P = 0.004], fat mass [2.07 (0.79; 3.34), P = 0.001], and waist [2.09 (0.39; 3.78), P = 0.01] in women but not men. Our data suggest that CRP is causally and positively related to BMI in women and that this is mainly due to fat mass. Results on the combined CRP-LEPR instrument suggest that leptin may play a role in the causal association between CRP and adiposity in women. Results in men were not significant.