Quantitative genetic study of amphiregulin and fractalkine circulating levels - potential markers of arthropathies

Objective: Amphiregulin (AREG) and Fractalkine (FRACT), are involved in a variety of normal and pathological processes, and are both suggested to be relevant to joint degeneration. The aims of the present study included (1) testing association between circulating levels of these biomarkers and joint pathologies, (2) evaluation of the putative genetic and familial factors' effect on AREG and FRACT variability. Design: The study was conducted in the family-based sample of 923 Caucasian individuals. Variance component analysis was used to assess contribution of genetic and environmental factors to variability of AREG and FRACT concentration. Results: The mean levels of FRACT were significantly higher in the affected group with arthropathies (synovial joints osteoarthritis (OA) and disc degenerative disease, DDD) then in the control group (P<0.0004). Circulating AREG levels were higher in DDD (P=0.0272). Genetic factors constituted the main source of the interindividual differences of the AREG and FRACT levels in our sample, and explained 29.68% and 41.68% of the total variation, respectively. The phenotypic correlation between AREG and FRACT was substantial (r=0.55, P=0.0001) and was associated with both common genetic and environmental factors. Specifically, 30% of the phenotypic correlation between AREG and FRACT was due to common genetic effects. Conclusions: Further studies are required to assess relevancy of FRACT to clinical diagnosis and prognosis of arthropathies, to investigate the mechanisms behind the observed phenotypic and genetic covariation among the studied biomarkers, and to explore specific genetic polymorphisms affecting AREG and FRACT variation.