Receptor Gene CAG Repeat Polymorphism Research Articles

Role of the Androgen Receptor Gene CAG Repeat Polymorphism on the Sequence of Pubertal Events and Adiposity in Girls with High Dehydroepiandrosterone Sulfate Level.

The androgen receptor (AR) harbors a variable repeat number of glutamine residues codified by (CAG)n, which seems to inversely affect AR transcriptional activity. We assessed whether (CAG)n affects the sequence of the androgen-sensitive pubertal events and body composition in prepubertal girls. Nested case-control study within the Growth and Obesity Cohort Study of 1196 low-middle income children (approximately 50% girls) from a university clinic in Santiago, Chile. Cases were girls with high dehydroepiandrosterone sulfate (DHEAS; >42μg/dL; HD) at age 7.0 (±0.4) years (n=58). On follow-up, 32 of them had thelarche (TB2) before the age of pubarche (PH2) and 26 had PH2 before the age of TB2. As controls, 107 age-matched girls with normal DHEAS (≤42μg/dL; ND) were selected. Methylation-weighted mean (CAG)n (mw[CAG]n) was calculated through X-chromosome methylation-sensitive enzyme restriction and polymerase chain reaction followed by automated capillary electrophoresis in peripheral blood DNA. Girls with HD and PH2 before the age of TB2 showed a trend to higher frequency (7/26, 26.9%) of mw(CAG)n <20 compared with ND girls (12/107; 11.2%; P=.087). Accordingly, a direct correlation between age of PH2 and mw(CAG)n was observed in HD (r=0.352; P=.007) and in ND girls (r=0.207; P=.033). Moreover, HD girls with mw(CAG)n less than 20 had lower waist circumference and waist/height ratio than HD girls with mw(CAG)n from 20 to less than 25 (P=.027 and P=.012, respectively) at age of DHEAS determination. Our results suggest that a greater transcriptional activity of theAR, given by short number of CAG repeats, might favor the onset of pubarche and reduce central adiposity in prepubertal girls with HD.

Association of androgen receptor gene CAG and GGN repeat polymorphism with cryptorchidism: A meta-analysis.

Researches on association between variations in the androgen receptor (AR) gene repeat polymorphisms and cryptorchidism (CO) had conflicting results. The aim of this meta-analysis was to analyse the potential effects of AR CAG and/or GGN repeat polymorphism on CO. Studies were independently appraised by two investigators on PubMed, Web of Science, EBSCO databases and Foreign Medical Retrieval System. Case-control studies with measurement of CAG and/or GGN repeat length were included. Weighted mean difference (WMD) and 95% confidence intervals (CIs) for the CAG or GGN repeat polymorphism and CO were calculated. Five reports were included in this analysis. Overall, no difference was identified between patients and fertile men in CAG repeat length. However, when the CO was divided into unilateral and bilateral, longer CAG repeat region was significantly associated with CO in bilateral group (WMD=0.74; 95% CI, 0.01-1.47; p<.05). In addition, GGN lengths were significantly higher in patients compared with those in controls (WMD=1.17; 95% CI, 0.28-2.06; p<.05). No obvious effect was found in the GGN length when compared unilateral or bilateral group with control respectively. The results in this meta-analysis indicated that AR CAG and GGN repeat polymorphisms may be an important pathogenesis of CO.

Androgen receptor gene CAG repeat polymorphism and ovarian cancer risk: A meta-analysis.

Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines. PubMed, Web of Science, EBSCO and other databases were searched up to September 15th 2016. Case control studies with clear definition of CAG repeat length and detailed genotype information were included. Two authors independently reviewed and extracted data. Pooled analysis and subgroup analysis stratified by ethnicity were performed for different genetic models. Begg's funnel plot and Egger's test were performed for publication bias estimation. Overall, there was no association between the AR CAG repeat polymorphism and ovarian cancer risk. However, short CAG repeat polymorphism was associated with increased ovarian cancer risk in African Americans and Chinese under the dominant model, whereas a reverse association was observed in Caucasians and Italians under the other three models. Our study results should be interpreted with caution. Further well-designed epidemiological and functional studies are needed to elucidate the role of AR in ovarian carcinogenesis.

Androgen receptor gene CAG repeat polymorphism and risk of isolated hypospadias: results from a meta-analysis.

Studies investigating the association between the CAG repeat polymorphism and the risk of isolated hypospadias have reported conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, CNKI, and Wanfang databases. Weighted mean difference and 95% confidence intervals for the CAG repeat polymorphism and isolated hypospadias were calculated using a random-effects model. Subgroup analyses were performed by race, study design, sample for DNA extraction, and hypospadias classifications. This meta-analysis included 6 case-control studies, including 444 isolated hypospadias cases and 727 controls. The results showed that patients with isolated hypospadias had longer CAG repeats in their androgen receptor gene sequence (weighted mean difference = 1.36, 95% confidence interval = 0.60-2.13; P = 0.0005). Similarly, stratified analyses also detected significant associations in all subgroups, excluding the group with severe hypospadias (weighted mean difference = 0.35, 95% confidence interval = -0.42-1.12; P = 0.38). This meta-analysis indicated that longer CAG repeats were associated with the risk of isolated hypospadias, and that longer CAG polymorphisms may be related to the etiology of isolated hypospadias. Future studies based on Asian and African-American patients should be performed to re-evaluate this association.

The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis.

Many studies have been carried out to confirm the relationship between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome (PCOS), without consistent results. Hence we conducted the current study to research this relationship. 224 Chinese Han women with PCOS and 223 in vitro fertilization and embryo transplantation (IVF-ET) infertile women with tubal factor or male infertility served as the controls were recruited in our study. PCR-based assays were applied to genotype the (CAG)n repeat alleles. A meta-analysis including 1,536 PCOS patients and 1,807 controls was conducted to produce a pooled estimate. We observed that the CAG bi-allelic mean lengths were similar in PCOS patients and controls (22.65 ± 2.5 vs. 23.09 ± 2.1, P = 0.116). When CAG bi-allelic were divided into two categories (mean repeats ≤22, >22), the short AR-CAG bi-allelic showed more frequent in PCOS group than in controls (56.25% vs 29.14%, P < 0.001). Further analysis presented that, in PCOS, there was a lower mean CAG repeat lengths in mean bi-allelic lengths (22.3 ± 2.5 vs. 23.9 ± 2.2, P = 0.008) and long bi-allelic lengths (24.3 ± 1.4 vs. 25.9 ± 1.6, P = 0.05) among patients with testosterone less than 0.7 ng/ml compared with those whose testosterone was more than 0.7 ng/ml. Besides, the testosterone were positively correlated with the CAG polymorphism (r = 0.237, P = 0.008), which accorded with our meta-analysis results. The distribution of AR-CAG allele differed between PCOS patients and controls, and polymorphism of CAG repeat lengths may contribute to hyperandrogenism in PCOS.

Androgen Receptor Gene CAG Repeat Polymorphism Independently Influences Recovery of Male Sexual Function After Testosterone Replacement Therapy in Postsurgical Hypogonadotropic Hypogonadism

Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function. In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies. Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT. Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number). Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found. The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported. On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed. Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies.

Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism

Background and aimsLittle is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism. Methods and resultsFourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed. ConclusionsIn male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT.

Androgen Receptor Gene CAG Repeat Polymorphism Regulates the Metabolic Effects of Testosterone Replacement Therapy in Male Postsurgical Hypogonadotropic Hypogonadism

Aim. To evaluate the independent role of androgen receptor (AR) gene CAG repeat polymorphism on metabolic effects of testosterone replacement therapy (TRT) in male postsurgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the TRT-related metabolic effects are combined with those deriving from concomitant administration of metabolically active pituitary-function replacement therapies. Methods. 15 men affected by postsurgical hypogonadotropic hypogonadism were evaluated before and after TRT. Cardiovascular risk factors (CVRFs), pituitary-dependent hormones, and AR gene CAG repeat polymorphism were considered. Results. Testosterone, insulin-like growth factor 1 (IGF-1), and estradiol were the only hormones, which varied significantly between the two phases. All CVRFs significantly improved after TRT. The number of CAG triplets was positively and significantly correlated with all the variations (Δ-) of CVRFs (except for a significant negative correlation with Δ-high-density lipoprotein); the opposite occurred between the latter and Δ-testosterone. No correlation between Δ-IGF-1 or estradiol and Δ-CVRFs was found. At multiple linear regression, after correction for Δ-testosterone, nearly all the associations between the number of CAG triplets and Δ-CVRFs were confirmed. Conclusions. In male postsurgical hypogonadotropic hypogonadism, shorter AR gene CAG tract length seems to yield greater metabolic improvement after TRT, independently of the effects of concomitant pituitary-function replacement therapies.

Negative association between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome? A systematic review and meta-analysis.

A number of studies focusing on the association between the exon 1 CAG repeat polymorphism of the androgen receptor (AR) gene and polycystic ovary syndrome (PCOS) have revealed conflicting results. The current systematic review and meta-analysis was conducted to quantify the strength of the association and to explore potential sources of heterogeneity that may have influenced the results. Studies matched to search terms from PubMed, EMBASE and HuGE Navigator published through to 31 January 2012 were retrieved. Data extraction from the included studies was carried out by two authors independently. Weighted mean differences (WMDs) of biallelic mean and odds ratios (ORs) of alleles and genotypes were pooled for meta-analysis. Sixteen articles reporting on 17 studies were included. In continuous data analysis, the summary WMD was -0.06 (95% confidence interval -0.29 to 0.16). In dichotomous data analysis, we divided the alleles into short and long alleles and calculated the summary ORs. No statistically significant results were identified by different comparison models or different cut-off point definitions. No publication bias was observed in continuous and dichotomous data analysis. In summary, the current systematic review and meta-analysis found that the AR CAG microsatellite repeat polymorphism is unlikely to be a major determining factor in the development of PCOS.

Androgen receptor gene CAG repeat polymorphism in longitudinal height and body composition in children and adolescents

The number of CAG repeats within the CAG repeat polymorphism of the androgen receptor (AR) gene correlates inversely with the transactivation of the receptor. We investigated the relationship between the AR CAG repeat polymorphism and longitudinal growth, puberty and body composition from prepuberty until young adult age. Observational study with repeated measurements. Two comparable young Dutch cohorts. The first cohort consisted of 226 subjects. Measurements were performed from 13 until 36 years of age. The second cohort consisted of 244 subjects. Measurements in this cohort were performed from 8 until 14 years of age. Associations between height, height velocity, weight, BMI, fat mass, fat-free mass and pubertal development and CAG repeat length were measured. Height-standard deviation scores (SDS) were inversely associated with AR CAG repeat length in boys at young, prepubertal and early pubertal age. This association diminishes in the following years and completely disappears after the age of 16 years. No associations were found with pubertal stage or any of the other parameters for body composition. AR CAG repeat length is inversely associated with longitudinal height in young boys, before the onset of puberty. During puberty, these differences disappear, possibly overruled by a strongly developing hypothalamic-pituitary-gonadal axis.

Androgen Receptor Gene CAG Repeat Polymorphism and Effect of Testosterone Therapy in Hypogonadal Men in Korea

Background: As the number of CAG repeats in the androgen receptor (AR) gene increases, transcriptional activities decrease and the effects of testosterone decline. In this study, we evaluated the importance of the CAG repeat polymorphism in regard to the ef fect/safety of testosterone therapy in hypogonadal Korean men. Methods: The number of CAG repeats was determined in 42 hypogonadal men who underwent testosterone therapy for more than 24 months between December 1999 and August 2007. Body mass index, lean body mass, body fat, bone mineral density, type I collagen N-telopeptide (NTx), osteocalcin, lipid profile, hematocrit and PSA levels prior to and after 24 months of testosterone therapy were identified in our medical record review. Results: Twenty-four months of testosterone therapy increased lean body mass, hematocrit, and PSA levels and reduced body fat, NTx, and HDL cholesterol levels. The mean number of CAG repeats in the AR gene was 23 ± 3 (range, 15-29) in hypogonadal Korean men. The number of CAG repeats was not found to be associated with changes in lean body mass, body fat, NTx, HDL cholesterol, hematocrit, or PSA levels during testosterone therapy. Conclusions: No association between the number of CAG repeats in the AR gene and the effect/safety of testosterone therapy was detected in hypogonadal Korean men. (Endocrinol Metab 26:225-231, 2011)

Androgen Receptor Gene CAG Repeat Polymorphism and Breast Cancer Risk in Iranian Women: A Case-Control Study

We investigated the association between polymorphic expansion of trinucleotide CAG repeats in androgen receptor (AR) gene and breast cancer risk among Iranian women in a matched case-control study. There was a strong overall association between per CAG repeat increments in average repeat length and the risk of the malignancy [OR=3.56; 95% CI, 2.80-5.29]. Women carrying one or two alleles with [CAG]n repeat ≥22 units were at increased risk of breast cancer [OR=2.03; 95% CI, 1.56-2.6]. The risk was significantly increased in homozygous longer repeats, versus homozygous alleles <22. We observed reduced risk of developing the tumor in positive familial breast cancer subjects carrying repeats ≥22 and 23. Homozygosity for the longer [CAG]n repeats may be linked to the increased breast cancer risk. In contrast to previous reports, longer AR [CAG]n repeat alleles may decline the risk among women with a familial breast cancer.

Association between androgen receptor gene CAG repeat polymorphism and breast cancer risk: a meta-analysis

Androgens have been hypothesized to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol and their binding to the estrogen receptor and/or androgen receptor (AR) in the breast. The CAG repeat polymorphism in AR exon 1 has been implicated in breast cancer risk; however, studies on the association between this polymorphism and breast cancer risk remain conflicting. In order to derive a more precise estimation of the relationship, a large population-based case-control study was performed. We found that a long CAG sequence has a protective effect on breast cancer using an a priori determined cutoff (< 22 or ≥ 22) in a dominant model analysis [SL-LL vs. SS, odds ratio (OR) = 0.86, 95% confidence intervals (CI): 0.67-1.10]. A similar result was obtained by analyzing seven detailed genotyping case-control studies by allele comparison in dominant and recessive models. However, larger scale primary study is required to further evaluate the interaction of AR CAG polymorphism and breast cancer risk.

Depressive Symptoms in Ageing Men and their Relation to the Androgen Receptor Gene CAG Repeat Polymorphism and Testosterone Levels

Depressive Symptoms in Ageing Men and their Relation to the Androgen Receptor Gene CAG Repeat Polymorphism and Testosterone Levels

Association Between Repeat Length of Exon 1 CAG Microsatellite in the Androgen Receptor and Bone Density in Men is Modulated by Sex Hormone Levels

In this study we examined whether the androgen receptor (AR) gene CAG repeat polymorphism and serum androgen levels are associated with bone mineral density (BMD) and changes in BMD during 2-3 years in 229 healthy men 41-76 years old. Microsatellite analysis was performed on an automated sequencer. Indices of bioavailable testosterone (free testosterone [FT] and free androgen index) were calculated. BMD was measured using both dual-energy Xray absorptiometry and quantitative ultrasound. All participants completed a questionnaire regarding major possible osteoporosis risk factors. In linear regression analysis there was a modest positive association, which was independent of age and body mass index (BMI), between AR repeat length and BMD at all sites. Although this association was significant independent of BMI, analyses in the subgroup of obese men (BMI > 30) did not reach significance, while the effect was enhanced when analyzing only nonobese men (BMI < or = 30). There was no association between the AR gene polymorphism and rate of bone loss, FT, and BMD or testosterone and bone loss. Interestingly, the association between AR and BMD was modified by total testosterone. The lowest age- and BMI-adjusted average femoral neck BMD was found among men in the lowest tertile for both AR repeat length and FT, whereas men within the higher categories of these variables displayed the highest BMD. In conclusion, there is a positive association between the AR CAG repeat polymorphism and BMD, which is modified by androgen levels in healthy men.

Androgen Receptor Gene CAG Repeat Polymorphism and X-Chromosome Inactivation in Children with Premature Adrenarche

There is variation in the adrenal androgen levels and clinical findings of children with premature adrenarche (PA). We hypothesized that androgen sensitivity, indicated by the length of CAG repeat in the X-chromosomal androgen receptor (AR) gene has a role in the polygenic pathogenesis of PA. We performed a cross-sectional association study among 73 Finnish Caucasian children with PA (10 boys and 63 girls) and 97 age- and gender-matched healthy controls (18 boys and 79 girls). AR gene methylation-weighted CAG(n)(mwCAG(n)) via CAG(n) length and X-chromosome inactivation analysis and clinical phenotype were determined. The study took place at a university hospital. PA subjects had significantly shorter mwCAG(n) than controls [mean difference (95% confidence interval); 0.76 (0.14-1.38); P = 0.017]. AR gene mwCAG(n) did not correlate with androgen or SHBG levels in either group. In children with PA, mwCAG(n) correlated positively with body mass index (BMI) (tau = 0.19; P = 0.02). The mean of mwCAG(n) was significantly shorter in PA children with lower BMI compared with PA children with higher BMI [BMI sd score < 0.79, n = 35, vs. BMI sd score > 0.79, n = 36; 1.13 (0.38-1.87), P = 0.004] and in PA children with lower BMI compared with healthy children with same BMI (P = 0.004). The AR gene CAG(n) polymorphism may have a significant role in the pathogenesis of PA, especially in lean children.

Androgen receptor gene CAG repeat polymorphism in women with polycystic ovary syndrome

To evaluate the role of the androgen receptor (AR) gene CAG repeat in women with polycystic ovary syndrome (PCOS). Case control study. University department of obstetrics and gynecology. Women with (n = 114) or without (n = 205) PCOS. Peripheral blood sampling was done for DNA analysis and serum hormone measurements. CAG repeat length and serum androgen levels. No statistically significant CAG repeat length differences were found between patients and controls. We conducted a detailed analysis after dividing PCOS patients according to their free testosterone levels. The high free testosterone group had a statistically significantly longer mean biallelic average (24.0 +/- 2.0 vs. 23.0 +/- 1.5), short (22.5 +/- 1.8 vs. 21.7 +/- 1.9), and long (25.5 +/- 2.9 vs. 24.4 +/- 1.9) allelic lengths than the normal free testosterone group. In PCOS patients, a statistically significant correlation was found between biallelic average length and free testosterone concentration, either unadjusted or after adjustment. The AR gene CAG repeat polymorphism may contribute to the serum concentration of free testosterone in PCOS patients. A subset of PCOS patients with relatively longer CAG repeats (less AR activity) tended to show a higher serum androgen concentration.

Shorter CAG repeats in the androgen receptor gene may enhance hyperandrogenicity in polycystic ovary syndrome

Background. The main goal of the present study was to assess the influence of the androgen receptor gene CAG repeat polymorphism on hyperandrogenism and its phenotypical features in patients with polycystic ovary syndrome (PCOS).Methods. CAG repeat lengths were analyzed in 97 oligo-anovulatory women with ultrasound features of PCOS. All individuals were assessed for endocrine parameters and their phenotypical features were recorded. These parameters were correlated with the CAG repeat lengths.Results. PCOS patients with a bi-allelic mean lower than 21 repeats had lower dihydrotestosterone levels (p = 0.007), lower androstenedione levels (p = 0.023), lower luteinizing hormone levels (p = 0.023), a lower luteinizing hormone/follicle-stimulating hormone ratio (p = 0.021) and the highest percentage of patients with acne and/or hirsutism (p = 0.021).Conclusions. Our findings support the hypothesis that the PCOS phenotype may result from either elevated androgen levels or an enhanced sensitivity to androgens caused by a more active androgen receptor.

Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men?

The androgen receptor (AR) gene contains a CAG repeat polymorphism coding for a polyglutamine chain, the length of which is inversely correlated with AR transcriptional activity. We explored whether this polymorphism modulates the activities of testosterone (T) related to body composition in elderly men. We performed cross-sectional analyses using data from a 4-year follow-up study in community-dwelling men aged 75-89 years (n=159). Body composition was assessed by dual-energy X-ray absorptiometry and its relation with T and the AR gene CAG repeat length was assessed by multiple linear regression analyses, adjusting for confounding and exploring effect modification. AR gene CAG repeat length was not directly related to body composition, either with or without adjustment for confounding variables like age, weight, total T or sex hormone binding globulin (SHBG) levels. However, exploration of effect modification showed that CAG repeat length modulated the relation between T and body composition (standardized regression coefficients of interaction term: beta=0.12, P<0.01 and beta=-0.09, P<0.05 for fat-free mass and fat mass respectively). These results were confirmed using similar models and data of mean T, SHBG and weight of the 2 years' preceding body composition assessment instead of data of the same year (beta=0.09, P<0.05 and beta=-0.09, P<0.05 respectively). These findings suggest that the AR gene CAG polymorphism contributes, albeit modestly, to the between-subject variation of T action on body composition in community-dwelling elderly men.

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

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. Longitudinal, population-based cohort study. 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. Poisson regression. 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. 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. 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.