The androgen receptor gene CAG polymorphism is associated with the severity of coronary artery disease in men

Alevizaki, Maria; Cimponeriu, Adriana; Garofallaki, M.; Sarika, Helen-Leda; Alevizaki, C. C.; Papamichael, Christos; Philippou, George; Anastasiou, Eleni; Lekakis, John; Mavrikakis, Myron

doi:10.1046/j.1365-2265.2003.01917.x

Cited by 69 publications

(92 citation statements)

References 57 publications

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“…Our results contrast with a recent study that found a weak association between short AR alleles with fewer CAG repeats and coronary artery stenosis but not with carotid intima thickness (20 ). That study, however, enrolled only a limited number of patients and controls (134 in total).…”

Section: Discussioncontrasting

confidence: 55%

The CAG Repeat Polymorphism in the Androgen Receptor Gene Is Associated with HDL-Cholesterol but Not with Coronary Atherosclerosis or Myocardial Infarction

et al. 2005

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Background: Age-adjusted morbidity and mortality rates from coronary heart disease (CHD) are higher in men than in women. Androgens are suspected to be responsible for the male disadvantage. The genomic effect of androgens is mediated by the androgen receptor (AR), which has a polymorphic CAG repeat in exon 1. The number of repeats is inversely related to the transcriptional activity of the AR on target genes. Methods: We investigated the association of this CAG repeat polymorphism with CHD and myocardial infarction (MI) in 2 independent case-control studies involving 544 Caucasian men. Results: The number of CAG repeats in the AR gene correlated significantly with HDL-cholesterol (HDL-C) in controls (r ‫؍‬ 0.21; P ‫؍‬ 0.015). This effect was independent of triglycerides, body mass index, alcohol intake, smoking, and age in a multiple regression model (R 2 ‫؍‬ 50%). Despite decreased HDL-C, lower CAG repeat numbers were not associated with increased risk for CHD (odds ratio ‫؍‬ 0.82; 95% confidence interval, 0.50 -1.36; P ‫؍‬ 0.44) or MI in carriers of AR genes with lower CAG repeat numbers (odds ratio ‫؍‬ 0.72; 95% confidence interval, 0.37-1.39; P ‫؍‬ 0.33). Conclusions: Shorter, more androgenic AR alleles with fewer CAG repeats are associated with lower HDL-C,

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Section: Discussioncontrasting

confidence: 55%

The CAG Repeat Polymorphism in the Androgen Receptor Gene Is Associated with HDL-Cholesterol but Not with Coronary Atherosclerosis or Myocardial Infarction

et al. 2005

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“…However, these women belonged to a highly selected group with possibly multiple predisposing factors and the observed effect was independent of other factors. Thus, although these results cannot be extrapolated to the general population, they show that within this group of women the genotype of sex hormone receptor may be of importance for the severity of CAD as it has been previously shown for men (19,25,57), obviously reflecting the long-term effects of sensitivity to hormonal action.…”

Section: Discussionmentioning

confidence: 75%

Severity of cardiovascular disease in postmenopausal women: associations with common estrogen receptor α polymorphic variants

et al. 2007

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Objective: Impaired estrogen action is a risk factor for coronary artery disease (CAD). Associations of CAD with estrogen receptor a (ERa) polymorphisms, which may influence sensitivity to estrogen, have been reported for men; the data concerning women are not conclusive. We investigated the association of common ERa polymorphisms with the severity of CAD and with metabolic and reproductive factors in postmenopausal women undergoing coronary angiography. Methods: ERa polymorphisms at positions c.454-397 TOC (PvuII) and c.454-351 AOG (XbaI) were studied in 157 women (age 45-88 years). The severity of CAD was assessed by the number of arteries with O50% stenosis in the angiography.Results: There was a significant association between the TT, TC, and CC genotypes (PvuII) and the severity of CAD (PZ0.008); similar results were obtained for the XbaI polymorphism (PZ0.021). These associations were independent of other risk factors for CAD. Women homozygous for the C allele had significantly higher triglyceride and insulin levels; they belonged more frequently to the group with a low number of births (n%1; PZ0.014, Fisher's exact). Conclusions: Common ERa polymorphisms may influence the severity of CAD in women undergoing coronary angiography, reflecting lifetime exposure to estrogen. Similar associations have been reported for men with CAD. These polymorphisms should probably be taken into account when associations with estrogenic actions are examined. European Journal of Endocrinology 156 489-496

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“…7 In 1 casecontrol study, men in the lowest CAG repeat quartile were more likely to have significant coronary heart disease than those in the highest quartile. 3 In contrast, no association between the number of CAG repeats and MI was observed in another case-control study in men, although those with fewer CAG repeats did have lower HDL levels. 8 Limitations of the present study include generalizability and potential biases.…”

Section: Rexrode Et Al Androgen Receptor Variation and Risk Of MI Andmentioning

confidence: 78%

“…Results were similar for cutpoints of Ն22 or Ն23 repeats. 3,6 In conditional logistic regression there was no significant association between repeat length and any of the end points, nor was any association observed when CAG repeat was modeled as a log-transformed continuous term. …”

mentioning

confidence: 99%

Genetic Variation of the Androgen Receptor and Risk of Myocardial Infarction and Ischemic Stroke in Women

Ridker

Hegener

Buring

et al. 2008

Stroke

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Background and Purpose-Androgen receptors (AR) are expressed in endothelial cells and vascular smooth-muscle cells.Some studies suggest an association between AR gene variation and risk of cardiovascular disease (CVD) in men; however, the relationship has not been examined in women. Methods-Six haplotype block-tagging single nucleotide polymorphisms (rs962458, rs6152, rs1204038, rs2361634, rs1337080, rs1337082), as well as the cysteine, adenine, guanine (CAG) microsatellite in exon 1, of the AR gene were evaluated among 300 white postmenopausal women who developed CVD (158 myocardial infarctions and 142 ischemic strokes) and an equal number of matched controls within the Women's Health Study. Results-Genotype distributions were similar between cases and controls, and genotypes were not significantly related to risk of CVD, myocardial infarctions or ischemic stroke in conditional logistic regression models. Seven common haplotypes were observed, but distributions did not differ between cases and controls nor were significant associations observed in logistic regression analysis. The median CAG repeat length was 21. In conditional logistic regression, there was no association between the number of alleles with CAG repeat length Ն21 (or Ն22) and risk of CVD, myocardial infarctions or ischemic stroke. [CAG] repeats in the amino-terminal domain, has been associated with higher testosterone levels in women, 1 as well as lower HDL levels, 2 impaired endothelial vasodilation, 2 and increased odds of coronary heart disease 3 in men. However, to the best of our knowledge, associations between AR genetic variation and cardiovascular disease (CVD) have not been evaluated in women. We examined 6 haplotype-tagging single nucleotide polymorphisms (htSNPs) and the CAG repeat microsatellite in exon 1 in a nested case-control study within the Women's Health Study (WHS). Conclusions-No Materials and Methods Study DesignA nested case-control study was performed within the WHS, a randomized trial of aspirin and vitamin E among 39 876 female health professionals. 4 Before randomization, 28 345 participants provided an EDTA-anticoagulated blood sample. Participants were free of known CVD and cancer at study entry. Yearly questionnaires ascertained newly developed CVD, and medical records were used to confirm events. 4 Before February 2004, 855 cases of first myocardial infarction or ischemic stroke occurred, with 458 meeting all our inclusion criteria (white postmenopausal women with data on smoking and hormone therapy). For 158, bloods were unavailable, leaving 300 cases for the present analysis. Compared to cases without blood, cases with blood available had similar BMI and hormone therapy use rates, but were slightly younger and less likely to smoke. For each case, a WHS control, who met these criteria but remained free from CVD until the case event, was matched by age, smoking status and use of postmenopausal hormone therapy.The study was approved by the Brigham and Women's Hospital Institutional Review Board for Human Subjects...

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The androgen receptor gene CAG polymorphism is associated with the severity of coronary artery disease in men

Cited by 69 publications

References 57 publications

The CAG Repeat Polymorphism in the Androgen Receptor Gene Is Associated with HDL-Cholesterol but Not with Coronary Atherosclerosis or Myocardial Infarction

The CAG Repeat Polymorphism in the Androgen Receptor Gene Is Associated with HDL-Cholesterol but Not with Coronary Atherosclerosis or Myocardial Infarction

Severity of cardiovascular disease in postmenopausal women: associations with common estrogen receptor α polymorphic variants

Genetic Variation of the Androgen Receptor and Risk of Myocardial Infarction and Ischemic Stroke in Women

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