A common variant near the PRL gene is associated with increased adiposity in males

A common variant (rs4712652) adjacent to the prolactin gene was recently associated with obesity using a genome-wide association study. The aim of this study was to replicate the association between rs4712652 and obesity and further examine if rs4712652 is associated with fat percentage and adiponectin levels in a population based Scandinavian cohort. rs4712652 was genotyped in 4879 participants (mean BMI 26.5 ± 4.5 kg/m2) from the population-based PPP-Botnia Study and related to BMI, fat percentage and adiponectin levels. We found that the risk A allele of rs4712652 is associated with increased BMI and fat percentage in males (P = 0.0047 and P = 0.025, respectively), but not in females (P = 0.98, P = 0.45). Male A allele carriers have a higher risk of being overweight with an OR of 1.16 (P = 0.025). While there was a significant negative correlation between adiponectin levels and fat percentage (r = −0.36; P = 0.039) in male carriers of the protective GG genotype, this correlation was lost in male carriers of the risk rs4712652 A allele (P = 0.33). Thus, the common SNP rs4712652 near the PRL gene seems to affect body fat and adiposity in a sex-specific fashion. It remains to be shown whether this is mediated by different prolactin concentrations or differences in tissue sensitivity to prolactin.