The androgen receptor CAG repeat polymorphism as a risk factor of low serum testosterone and its cardiometabolic effects in men

R. Haring, Florian Ernst, Claudia Schurmann, Georg Homuth, Uwe Völker, Henry Völzke, M A Nauck, Henri Wallaschofski

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15 Citations (Scopus)

Abstract

Previous studies reported correlations of CAG repeat length with sex hormone serum concentrations and cardiometabolic risk factors, but were limited by small cross-sectional samples. We used data of 1859 men aged 20-79years from the population-based Study of Health in Pomerania (SHIP) to investigate the direct and modulating effects of CAG repeat length on androgen action and cardiometabolic risk factors. We performed cross-sectional and longitudinal linear and Poisson regression models adjusted for age, smoking, physical activity, alcohol consumption and body mass index. The CAG repeat length was categorized into quartiles and low total testosterone (TT) defined according to the age-specific (by decades) 10th percentile, respectively. Age-adjusted cross-sectional linear regression models showed a positive association between CAG repeat length and serum testosterone concentrations [β coefficient for TT, 0.099 (p=0.028) and for free T, 0.002 (p=0.001), respectively]. After a 5.0year median follow-up period, men with CAG repeat length in the lowest quartile had an increased risk of incident low TT concentrations [relative risk (RR), 2.31; 95% confidence interval (CI), 1.18-4.55]. We found no direct association between CAG repeat length and cardiometabolic risk factors in cross-sectional and longitudinal multivariable linear regression analyses; whereas men with longer CAG repeat length and low TT concentrations showed the highest risk of incident MetS (RR, 1.51; 95% CI, 1.05-2.16). CAG repeat length is a risk factor of incident low TT concentrations and a contributing factor of testosterone-related cardiometabolic effects. The added clinical value of a combined assessment of CAG repeat length and serum TT concentrations merits further investigation.

Original languageEnglish
Pages (from-to)511-520
Number of pages10
JournalInternational Journal of Andrology
Volume35
Issue number4
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

Keywords

  • CAG repeat
  • Cardiometabolic risk factors
  • Longitudinal population-based cohort
  • Metabolic syndrome
  • Testosterone

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