However, after scrutiny of the included studies, we could find that most of the studies included for the analysis of aggrecan gene recruited subjects in the absence of other risk factors such as obesity, smoking, heavy physical occupations [11], [16], [18], [35], which were rarely mentioned in the studies for the analysis of VDR gene polymorphisms. This evidence concerns the gene ACAN and obesity due to melanocortin 4 receptor deficiency.