Androgen receptor gene polymorphism and the metabolic syndrome in 60–80 years old Norwegian men

Abstract

The metabolic syndrome (MS) includes a clustering of metabolic derangements. Low testosterone levels have been shown to be associated with both components of MS and MS per se. As most androgen-related effects are mediated thorough the androgen receptor (AR), we wanted to investigate to which degree the AR CAG and GGN repeat polymorphisms might be related to MS. Sixty-eight men, 60-80 years old, with subnormal total testosterone levels (<or=11.0 nmol/L) and 104 men with normal levels (>11.0 nmol/L), participating in a nested case-control study were investigated in this study. Body weight, height, waist circumferences and blood pressure were measured. Fasting blood samples were drawn and an oral glucose tolerance test (OGTT) was performed. The CAG and GGN polymorphisms in the AR gene were determined by direct sequencing of leucocyte DNA. Men with MS had lower CAG repeat number than healthy men (p = 0.007). There were, however, no difference in CAG or GGN repeats length between the groups with subnormal or normal testosterone concentrations. In cross-sectional analyses, men with CAG repeat lengths <or= 21 had significantly higher fasting glucose, C-peptide and glycosylated haemoglobin (HbA1c) levels (all p < 0.05). In multiple regression analyses, CAG repeat length was an inverse and independent predictor of glucose after an OGTT and of HbA1c levels. We also found that men with more than one component of MS had shorter CAG repeat number (p for trend 0.013) than those with only one component. In conclusion, there were no associations with GGN repeat length, while short CAG repeat length seems to be associated with increased risk of MS.