AB018. Androgen receptor CAG repeat length polymorphism as a risk factor of late onset hypogonadism/metabolic syndrome in a Korean male population

Background: Androgen receptor (AR) CAG polymorphism modulates the effect of testosterone in target organs. However, correlation between AR CAG repeat length and clinical features of late onset hypogonadism (LOH) is unclear and there are only few studies from Asian population. In this study, we explored the relationship of AR CAG repeat length polymorphism with LOH and metabolic syndrome (MS) in Korean male population.

Methods: The association between AR CAG repeat length and LOH, MS were studied in a total of 600 Korean men from 2013 to 2015. LOH was diagnosed by serum testosterone level of <3.5 ng/mL and ADAM questionnaire. AR CAG repeat length was determined by microsatellite fragment sizing. MS was diagnosed with NCEP criteria ATP III. Clinical factors and questionnaire related with LOH [patient health questionnaire-9 (PHQ), aging male symptom scale (AMS), and international index of erectile function (IIEF-5)] were analyzed with AR CAG repeat length.

Results: Mean age of the patients was 61.2±10.9 years and mean AR CAG repeat length was 22.2±5.1. Mean serum testosterone levels was 2.6±0.7 in men with LOH and 6.0±2.0 in men without LOH, respectively. A total of 33 men (12.5%) were diagnosed with LOH. Men with LOH showed significant longer AR CAG repeat length compared with men without LOH (26.1 vs. 21.6, P<0.001). As CAG repeat length increased, AMS total and AMS psychotic/somatic/sexual subscore increased (r=0.219, r=0.168, r=0.160, r=0.241) (P=0.001, P=0.006, P=0.001, P=0.001) and IIEF-5 score decreased, significantly (r=−0.187, P=0.002). In multivariate analysis showed that CAG and total AMS score were independently associated with LOH. (OR =1.3, 0.9, P<0.001, 0.005, respectively) Men with MS showed significant longer AR CAG repeat length compared with men without MS (26.2 vs. 21.4, P<0.001). As CAG repeat length increased, number of components of NCEP criteria increased, significantly (R2 =0.119, P=0.001). AR CAG repeat length showed significant correlation with HDL (r=−0.244, P<0.001), triglyceride (r=0.276, P<0.001), HbA1c (r=0.201, P<0.001). In multivariate analysis, CAG repeat length, waist circumference and HDL were independent risk factors of MS.

Conclusions: In conclusion, AR CAG repeat length was associated with prevalence of LOH and clinical symptoms of LOH in a Korean male population. Longer CAG repeat length was identified as one of the risk factor of LOH and MS in Korean male.

Keywords: Androgen receptor (AR); hypogonadism syndrome; metabolic