102 Influence of Genetic Variation in the Androgen Receptor on the Risk of Cardiovascular Disease in Aging Men

Abstract

Controversy still exists regarding the effect of hypogonadism on cardiovascular (CV) health and the safety of testosterone replacement therapy (TRT). We hypothesized that differences in androgen sensitivity, a function of the number of trinucleotide repeats on the androgen receptor (AR) gene, may result in greater reactivity to age-related testosterone changes and increased risk of CV disease. Participants were men from the Vietnam Era Twin Study of Aging (N=696). Mean age was 56.4 years (range:51-60). Average waking, salivary free-testosterone level was acquired on 3 non-consecutive days. Low testosterone (low-T) was defined as being ≥ 1 SD below the mean. The AR gene CAG repeat length was derived using polymerase chain reaction (PCR) fragment analysis and Sanger sequencing. Average repeat length was 22 (range:8-37). CV disease was assessed by self-report and medication data. We tested the interaction between low testosterone (low-T) and CAG repeat length while controlling for age, ethnicity, smoking status, BMI, hypertension, diabetes, and the correlated nature of the twin data.