OBJECTIVE: The role of androgens in the pathogenesis of coronary artery disease (CAD) remains controversial. The length of the polyglutamine stretch of the transactivation domain (CAG repeat) of the androgen receptor (AR) inversely affects androgen activity. The aim of this study was to investigate the effect of this polymorphism of the AR gene in the extent of CAD in male patients. DESIGN AND PATIENTS: The relationship of the length of the AR gene CAG repeat on the severity of CAD was examined in 131 men (36-86 years old) undergoing coronary angiography. MEASUREMENTS: The severity of CAD was assessed by the number (0-3) of coronary vessels with > 50% reduction in the luminal diameter. The interaction of the AR gene polymorphism with the intima media thickness (IMT) of peripheral arteries and serum levels of sex steroids, insulin and biochemical parameters were also studied. RESULTS: The upper quartile of CAG length (range 9-30) was > or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs. 27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between the AR gene repeat length and serum testosterone. Oestradiol levels were significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had significant CAD (i.e. one to three arteries with stenosis) more frequently (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This association was independent of age and BMI. The IMT of peripheral arteries, lipid parameters, basal insulin resistance, blood pressure and family history for early CAD, did not differ according to AR length. CONCLUSIONS: The shorter CAG repeat of the AR gene is associated with more severe CAD, which suggests a role for the sensitivity to androgens in the increased frequency of CAD in males. In addition, a protective role of endogenous oestrogen, which is higher in the longAR subgroup, can contribute to the observed difference.
OBJECTIVE: The role of androgens in the pathogenesis of coronary artery disease (CAD) remains controversial. The length of the polyglutamine stretch of the transactivation domain (CAG repeat) of the androgen receptor (AR) inversely affects androgen activity. The aim of this study was to investigate the effect of this polymorphism of the AR gene in the extent of CAD in male patients. DESIGN AND PATIENTS: The relationship of the length of the AR gene CAG repeat on the severity of CAD was examined in 131 men (36-86 years old) undergoing coronary angiography. MEASUREMENTS: The severity of CAD was assessed by the number (0-3) of coronary vessels with > 50% reduction in the luminal diameter. The interaction of the AR gene polymorphism with the intima media thickness (IMT) of peripheral arteries and serum levels of sex steroids, insulin and biochemical parameters were also studied. RESULTS: The upper quartile of CAG length (range 9-30) was > or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs. 27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between the AR gene repeat length and serum testosterone. Oestradiol levels were significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had significant CAD (i.e. one to three arteries with stenosis) more frequently (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This association was independent of age and BMI. The IMT of peripheral arteries, lipid parameters, basal insulin resistance, blood pressure and family history for early CAD, did not differ according to AR length. CONCLUSIONS: The shorter CAG repeat of the AR gene is associated with more severe CAD, which suggests a role for the sensitivity to androgens in the increased frequency of CAD in males. In addition, a protective role of endogenous oestrogen, which is higher in the longAR subgroup, can contribute to the observed difference.
Authors: Sara Lindström; Jing Ma; David Altshuler; Edward Giovannucci; Elio Riboli; Demetrius Albanes; Naomi E Allen; Sonja I Berndt; Heiner Boeing; H Bas Bueno-de-Mesquita; Stephen J Chanock; Alison M Dunning; Heather Spencer Feigelson; J Michael Gaziano; Christopher A Haiman; Richard B Hayes; Brian E Henderson; David J Hunter; Rudolf Kaaks; Laurence N Kolonel; Loic Le Marchand; Carmen Martínez; Kim Overvad; Afshan Siddiq; Meir Stampfer; Pär Stattin; Daniel O Stram; Michael J Thun; Dimitrios Trichopoulos; Rosario Tumino; Jarmo Virtamo; Stephanie J Weinstein; Meredith Yeager; Peter Kraft; Matthew L Freedman Journal: J Clin Endocrinol Metab Date: 2010-06-09 Impact factor: 5.958
Authors: Calen P Ryan; Thomas W McDade; Lee T Gettler; Dan T A Eisenberg; Margarita Rzhetskaya; M Geoffey Hayes; Christopher W Kuzawa Journal: Am J Hum Biol Date: 2016-07-15 Impact factor: 1.937
Authors: Lois B Travis; Clair Beard; James M Allan; Alv A Dahl; Darren R Feldman; Jan Oldenburg; Gedske Daugaard; Jennifer L Kelly; M Eileen Dolan; Robyn Hannigan; Louis S Constine; Kevin C Oeffinger; Paul Okunieff; Greg Armstrong; David Wiljer; Robert C Miller; Jourik A Gietema; Flora E van Leeuwen; Jacqueline P Williams; Craig R Nichols; Lawrence H Einhorn; Sophie D Fossa Journal: J Natl Cancer Inst Date: 2010-06-28 Impact factor: 13.506
Authors: Tamra E Meyer; Thomas G O'Brien; Gabriella Andreotti; Kai Yu; Qizhai Li; Yu-Tang Gao; Asif Rashid; Ming-Chang Shen; Bing-Sheng Wang; Tian-Quan Han; Bai-He Zhang; Shelley Niwa; Joseph F Fraumeni; Ann W Hsing Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-03-03 Impact factor: 4.254
Authors: C Doukas; K Saltiki; A Mantzou; A Cimponeriu; K Terzidis; L Sarika; M Mavrikakis; P Sfikakis; M Alevizaki Journal: Rheumatol Int Date: 2012-03-31 Impact factor: 2.631
Authors: S F Yu; T T Cheng; Y H Hsu; H M Lai; Y C Chen; C K Chiu; K M Lin; C Chang; C J Chen; H Y Kang Journal: Clin Rheumatol Date: 2007-04-13 Impact factor: 2.980