Genetic and environmental determinants of circulating resistin level in a community-based sample

Resistin is a hormone secreted by adipose tissue, monocytes, bone marrow, and other tissues. It was also proclaimed as an important link between obesity and diabetes. The main objective of this study was to elucidate the contribution of a number of endogenous factors, such as sex, age, obesity characteristics, and genetic effects to the production of resistin in apparently healthy individuals. We also tested the possible relationships between circulating levels of resistin and other adipokines (leptin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)).

The plasma levels of studied adipokines were determined by enzyme-linked immunoassay in pedigree-based sample (n = 616), and subjected to model-based quantitative genetic analysis.

Resistin levels were significantly higher in women than in men (3.60 +/- 2.53 vs 3.15 +/- 2.48 ng/ml, P < 0.001), and varied independently of age in either sex. Statistical-genetic analysis revealed significant familial correlations (P < 0.01) for resistin. Adjusted for covariates, 66.38 +/- 10.28% of the resistin variation was attributable to putative genetic factors. A relatively small portion of the resistin variation (11.54 +/- 5.77%) was attributable to sharing a common household environment. The remaining variation, 22.12 +/- 17.69% was due to random environmental (i.e., unmeasured non-additive genetic) effects. The results of our analysis showed modest significant correlation of resistin with TNF-alpha and IL-6, and only in some groups; thus, while resistin was correlated with TNF-alpha in men, the correlation with IL-6 was significant only in the post-menopausal women group.

Our observations indicate that resistin is strongly influenced by genetic factors. The high heritability estimates for resistin concentrations clearly suggest the continuing need for further molecular genetic investigations.