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The androgen receptor gene CAG repeat polymorphism does not predict increased risk of heart disease: longitudinal results from the Massachusetts Male Ageing Study


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Objective  Sex steroids may contribute to the increased prevalence of heart disease (HD) in men compared to age-matched women. Androgens bind their cognate receptor, and androgen action is inversely proportional to the number of CAG repeats in exon 1 of the androgen receptor gene. Longer, less androgenic CAG repeats have been associated with higher high-density lipoprotein (HDL) levels, which might protect against HD. Therefore, we hypothesized that CAG repeat length contributes to HD risk in men.

Design  Longitudinal, population-based cohort study.

Population  One thousand thirty-four participants from the Massachusetts Male Ageing Study, a cohort of 1709 men from the Boston area, aged 40–70, observed at three time points over 15 years.

Methods  Poisson regression.

Measurements  Heart disease was determined by self-report, medical records or from the National Death Index. Lipids and hormones were measured from blood samples drawn at each time point. CAG repeat length was assessed from DNA collected at the second time point.

Results  We found no increased risk of HD associated with CAG repeat length in our analyses. Moreover, CAG repeat length was not related to body mass index, HDL, low-density lipoprotein or waist to hip ratio in this cohort; nor did CAG repeat length predict changes in these variables over 15 years of follow-up.

Conclusions  In contrast to previous smaller, cross-sectional analyses, in this large cohort of community-dwelling men followed over 15 years, CAG repeat length was not related to the incidence or prevalence of HD or alterations in HDL. If androgens impact HD risk, this effect is unlikely to be mediated via CAG repeat length.