Specifically, the LEP A19G mutation in Lepob and LEPR Q223R, K109R and K656N mutations in LepR have been proposed to be associated with obesity; however, the first results obtained from a meta-analysis of published studies were not able to establish a strong link between leptin and LepR polymorphisms and obesity [291]. This evidence concerns the gene LEPR and obesity due to melanocortin 4 receptor deficiency.