Androgen Receptor Gene Repeat Polymorphism, Leptin And Fat Mass In Young Men And Women

Abstract

The exon-1 of the androgen receptor (AR) gene contains two length polymorphisms which modify either the amount of AR protein inside the cell (GGNn, polyglycine) or its transcriptional activity (CAGn, polyglutamine). Shorter CAG and/or GGN repeats provide stronger androgen signaling, and vice versa. On the other hand, androgen levels are inversely associated with fat mass. PURPOSE: To test the hypothesis that CAG and GGN repeat AR polymorphism influences body fat and serum leptin concentrations. METHODS: The length of CAG and GGN repeats was determined by PCR and fragment length analysis, serum leptin concentration by ELISA, and fat mass with DEXA in 282 men (28.6 ± 7.6 years) and 61 women (25.5 ± 6.7 years). All subjects were healthy and physically active. Individuals were grouped as CAG short (CAGs) if harboring repeat lengths of ≤21 in men and ≤22 in women, and CAG long (CAGL) if CAG >21 in men and >22 in women. GGN was considered short (GGNs) or long (GGNL) if GGN ≤23 or >23 in men and women. RESULTS: There was no relationship between GGN and CAG repeat length and serum leptin concentration neither in women nor men. CAGs and CAGL groups had similar leptin concentrations, and GGNs and GGNL groups as well. There was no relationship between CAG repeat length and whole body fat mass, percentage of fat mass accumulated in the trunk region and percentage of body fat neither in men nor women. The GGN repeat length was not associated to fat mass or to the percentage of body fat in men. However, in women, there was a linear relationship between the length of GGN repeat microsatellite and the percentage of body fat (% fat=2.16xGGN -21.73, r=0.31, P<0.05) and a trend for a similar relationship between whole body fat mass and GGN repeat length (fat mass (kg) = 1.41xGGN - 14.97, r=0.22, P=0.09). No association between CAG or GGN repeat length and trunk fat accumulation was observed. CONCLUSIONS: A long repeat GGN polymorphism is positively associated with increased percentage of body fat in physically active young women. Supported by Ministerio de Educación y Ciencia (DEP2006-56076-C06-04/ACTI), Consejería de Educación, Cultura y Deportes del Gob. de Canarias (2006/179 0001 and FEDER), Proyecto Interreg IIIB BIOPOLIS, Fundación del Instituto Canario de Investigación del Cáncer (FICIC), Cabildo de Gran Canaria, Cabildo de Tenerife and La Caja de Canarias.