Context Leptin and C-reactive protein (CRP) concentrations are increased in inflammation, and both have been linked to increased risk for cardiovascular diseases.

Objective To explore in a population based sample whether the relation between leptin CRP is independent of obesity level and whether genetic causes of CRP elevation contribute to leptin levels.

Design Population based study including 1,862 young adults (971 women; 891 men) aged 24 to 39 years.

Setting Five centers in Finland.

Main Outcome Measures Associations between leptin and CRP adjusted for obesity indices, risk factors, genetic variables and life-style variables.

Results Women had 3.0 fold higher median concentrations of leptin (12.5 vs. 4.1 ng/mL) and 1.3 fold higher median concentrations of CRP (0.75 vs. 0.56 mg/L) than men (p<0.0001 in both comparisons). In univariate analyses, CRP and leptin were significantly intercorrelated (r=0.47, p<0.0001 for women, r=0.46, p<0.0001 for men). In multiple regression analysis including age, body mass index, waist circumference, insulin, lipids, systolic and diastolic blood pressures, smoking status and use of oral contraceptives in women, leptin was the main determinant of CRP in men (p<0.0001) and the second most important determinant in women (p<0.0001). A Mendelian randomization test based on genetic variants in the CRP gene (5 SNP's) provided no support for CRP as a causal agent for leptin.

Conclusions Leptin, obesity and oral contraceptive use in women were the main factors related to CRP. The relation between leptin and CRP was independent of obesity and cardiovascular risk factors.