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Genetic factors substantially influence inter-individual differences in body shape and configuration in two studied samples. However, further studies are needed to clarify the extent of pleiotropy and epigenetic effects on various facets of the human physique.

Objectives: To determine the ranges of variation of circulating receptor activator of nuclear factor-kB ligand (RANKL)/osteoprotegerin (OPG)/macrophage-colony stimulating factor (M-CSF) and to ascertain their potential relationships with age, sex and menopausal status in women, and with sex hormones in a population-based healthy cohort. Subjects and methods: Blood samples were collected with EDTA after an overnight fast. The plasma levels of each of the above biochemical indices were measured by ELISA in a total of 566 apparently healthy individuals aged 18-75 years. Results: The plasma concentrations of cytokine molecules in the entire sample ranged from 674 to 4929 pg/ml for OPG, from 105 to 4468 pg/ml for soluble RANKL (sRANKL), and from 187 to 7604 pg/ml for M-CSF. The OPG levels demonstrated a clear positive correlation with age in both sexes (r ¼ 0.42 and 0.43, P , 0.001, for men and women respectively). Application of the two-interval mathematical model revealed that in females OPG levels were age-independent until age 42, but then showed clear and significant correlation with age (r ¼ 0.48, P , 0.001). As a result, young females (before 42 years) had a substantially lower average OPG level, 1377.8^327.68 pg/ml, in comparison with older women, 1666.02^397.14 pg/ml. The M-CSF correlation with age was significantly greater in women (r ¼ 0.29, P , 0.001) compared with men (r ¼ 0.17, P , 0.01). Significant negative correlations between plasma levels of both OPG and M-CSF with estradiol concentrations were observed in women (r ¼ 2 0.39, P , 0.01; r ¼ 20.25, P , 0.001 respectively). sRANKL did not correlate with either age or sex hormones in either women or men. Conclusion: Age and sex affect differently the interindividual variation of OPG, RANKL and M-CSF. Our observations could form the basis for further research to establish provisional reference limits for OPG and RANKL, which are potential markers for benign and malignant processes in bone.European Journal of Endocrinology 150 305-311

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The results provide evidence that putative genetic factors involved in regulation of HGF variation contribute also significantly to variation of the obesity and BP. It is possible that the familial resemblance for WHR and the SBP correlation in the studied sample is affected substantially by genetic factors regulating circulating HGF levels.