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AR Gene (ar + gene)
Selected AbstractsAldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patientsDIABETIC MEDICINE, Issue 8 2006A. Watarai Abstract Aims The aldose reductase (AR) gene, a rate-limiting enzyme of the polyol pathway, has been investigated as a candidate gene in determining susceptibility to diabetic microangiopathy. However, the association of the AR gene with diabetic macroangiopathy has not been investigated. Therefore, the present study was conducted to determine whether genetic variations of AR may determine susceptibility to diabetic macroangiopathy. Methods There were 378 Type 2 diabetic patients enrolled in this study. A single nucleotide polymorphism in the promoter region (C-106T) was genotyped and the AR protein content of erythrocytes measured by ELISA. Results There were no significant differences in genotypic or allelic distribution in patients with or without ischaemic heart diseases, but there was a significant increase in the frequency of the CT + TT genotype and T allele in patients with stroke (P = 0.019 and P = 0.012). The erythrocyte AR protein content was increased in patients with the CT and TT genotype compared with those with the CC genotype. After adjustment for age, duration of diabetes, body mass index, systolic blood pressure, HbA1c, and serum creatinine, triglycerides, and total cholesterol in multivariate logistic-regression models, the association between this AR genotype and stroke remained significant. Conclusions Our results suggest that the CT or TT genotype of the AR gene might be a genetic marker of susceptibility to stroke in Type 2 diabetic patients. This observation might contribute to the development of strategies for the prevention of stroke in Type 2 diabetic patients. [source] Androgen receptor function is modulated by the tissue-specific AR45 variantFEBS JOURNAL, Issue 1 2005Isabelle Ahrens-Fath A naturally occurring variant of the human androgen receptor (AR) named AR45 has been identified. It lacks the entire region encoded by exon 1 of the AR gene and is composed of the AR DNA-binding domain, hinge region and ligand-binding domain, preceded by a novel seven amino-acid long N-terminal extension. A survey of human tissues revealed that AR45 was expressed mainly in heart and skeletal muscle. In cotransfection experiments, AR45 inhibited AR function, an effect necessitating intact DNA- and ligand-binding properties. Overexpression of AR45 reduced the proliferation rate of the androgen-dependent LNCaP cells, in line with the repressive effects of AR45 on AR growth-promoting function. AR45 interacted with the AR N-terminal domain in two-hybrid assays, suggesting that AR inhibition was due to the formation of AR,AR45 heterodimers. Under conditions where the transcriptional coactivator TIF2 or the oncogene ,-catenin were overexpressed, AR45 stimulated androgen-dependent promoters in presence of dihydrotestosterone. AR45 activity was triggered additionally by the adrenal androgen androstenedione in presence of exogenous TIF2. Altogether, the data suggest an important role of AR45 in modulating AR function and add a novel level of complexity to the mode of action of androgens. [source] Androgen receptor exon 1 CAG repeat length and risk of hepatocellular carcinoma in womenHEPATOLOGY, Issue 1 2002Ming-Whei Yu The androgen receptor (AR) gene is localized on chromosome X, and shorter CAG repeats in exon 1 of the AR gene were recently suggested to increase hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk among men. To examine whether the relationship between the AR-CAG repeats and HCC was also evident among women, we conducted a case-control study in Taiwan. The number of AR-CAG repeats was determined for 238 women with HCC and 354 unrelated control subjects (comprising 188 first-degree and 166 nonbiological relatives) selected from female relatives of patients with HCC. Women harboring 2 AR alleles with more than 23 CAG repeats had an increased risk of HCC (age-adjusted odds ratio [OR], 1.82; 95% CI, 1.06-3.14), compared with women with only short alleles or a single long allele. The association between harboring 2 AR alleles containing longer CAG repeats and HCC was more striking among HBV carriers (age-adjusted OR for more than 22 repeats, 2.23; 95% CI, 1.14-4.34) and particularly prominent among HBV carriers under age 53 years (age-adjusted OR, 3.16; 95% CI, 1.13-8.82). When CAG repeats were analyzed as a continuous variable, the increase in HCC risk associated with each incremental repeat in the shorter of 2 alleles in a given genotype was statistically significant among women with a first-degree relative with HCC (age-adjusted OR, 1.18; 95% CI, 1.01-1.37). No such relationship was detected among women without the family history. In conclusion, our observations suggest that the AR-CAG alleles may contribute to HCC predisposition among women through a mechanism different from that for men. [source] Androgen receptor gene polymorphism and the metabolic syndrome in 60,80 years old Norwegian menINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2010Paal André Skjærpe Summary The metabolic syndrome (MS) includes a clustering of metabolic derangements. Low testosterone levels have been shown to be associated with both components of MS and MS per se. As most androgen-related effects are mediated thorough the androgen receptor (AR), we wanted to investigate to which degree the AR CAG and GGN repeat polymorphisms might be related to MS. Sixty-eight men, 60,80 years old, with subnormal total testosterone levels (,11.0 nmol/L) and 104 men with normal levels (>11.0 nmol/L), participating in a nested case,control study were investigated in this study. Body weight, height, waist circumferences and blood pressure were measured. Fasting blood samples were drawn and an oral glucose tolerance test (OGTT) was performed. The CAG and GGN polymorphisms in the AR gene were determined by direct sequencing of leucocyte DNA. Men with MS had lower CAG repeat number than healthy men (p = 0.007). There were, however, no difference in CAG or GGN repeats length between the groups with subnormal or normal testosterone concentrations. In cross-sectional analyses, men with CAG repeat lengths , 21 had significantly higher fasting glucose, C-peptide and glycosylated haemoglobin (HbA1c) levels (all p < 0.05). In multiple regression analyses, CAG repeat length was an inverse and independent predictor of glucose after an OGTT and of HbA1c levels. We also found that men with more than one component of MS had shorter CAG repeat number (p for trend 0.013) than those with only one component. In conclusion, there were no associations with GGN repeat length, while short CAG repeat length seems to be associated with increased risk of MS. [source] The CAG repeat polymorphism within the androgen receptor gene and maleness,INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2003Michael Zitzmann Summary The androgen testosterone and its metabolite dihydrotestosterone exert their effects on gene expression and thus effect maleness via the androgen receptor (AR). A diverse range of clinical conditions starting with complete androgen insensitivity has been correlated with mutations in the AR. Subtle modulations of the transcriptional activity induced by the AR have also been observed and frequently assigned to a polyglutamine stretch of variable length within the N-terminal domain of the receptor. This stretch is encoded by a variable number of CAG triplets in exon 1 of the AR gene located on the X chromosome. First observations of pathologically elongated AR CAG repeats in patients with X-linked spino-bulbar muscular atrophy showing marked hypoandrogenic traits were supplemented by partially conflicting findings of statistical significance also within the normal range of CAG repeat length: an involvement of prostate tissue, spermatogenesis, bone density, hair growth, cardiovascular risk factors and psychological factors has been demonstrated. The highly polymorphic nature of glutamine residues within the AR protein implies a subtle gradation of androgenicity among individuals within an environment of normal testosterone levels providing relevant ligand binding to ARs. This modulation of androgen effects may be small but continuously present during a man's lifetime and, hence, exerts effects that are measurable in many tissues as various degrees of androgenicity and represents a relevant effector of maleness. It remains to be elucidated whether these insights are important enough to become part of individually useful laboratory assessments. [source] Osteoblast Deletion of Exon 3 of the Androgen Receptor Gene Results in Trabecular Bone Loss in Adult Male Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2007Amanda J Notini Abstract The mechanism of androgen action on bone was studied in male mice with the AR deleted in mature osteoblasts. These mice had decreased trabecular bone volume associated with a decrease in trabecular number, suggesting that androgens may act directly on osteoblasts to maintain trabecular bone. Introduction: Androgens modulate bone cell activity and are important for the maintenance of bone mass. However, the mechanisms by which they exert these actions on bone remain poorly defined. The aim of this study was to investigate the role of androgens acting through the classical androgen receptor (AR) signaling pathways (i.e., DNA-binding dependent pathways) in osteoblasts using male mice in which exon 3 of the AR gene was deleted specifically in mature osteoblasts. Materials and Methods: Mice with a floxed exon 3 of the AR gene were bred with Col 2.3-cre transgenic mice, in which Cre recombinase is expressed in mineralizing osteoblasts. The skeletal phenotype of mutant mice was assessed by histomorphometry and quantitative ,CT at 6, 12, and 32 weeks of age (n = 8 per group). Wildtype, hemizygous exon 3 floxed and hemizygous Col 2.3-cre male littermates were used as controls. Data were analyzed by one-way ANOVA and Tukey's posthoc test. Results: ,CT analysis of the fifth lumbar vertebral body showed that these mice had reduced trabecular bone volume (p < 0.05) at 32 weeks of age compared with controls. This was associated with a decrease in trabecular number (p < 0.01) at 12 and 32 weeks of age, suggesting increased bone resorption. These effects were accompanied by a reduction in connectivity density (p < 0.01) and an increase in trabecular separation (p < 0.01). A similar pattern of trabecular bone loss was observed in the distal femoral metaphysis at 32 weeks of age. Conclusions: These findings show that inactivation of the DNA binding,dependent functions of the AR, specifically in mature osteoblasts in male mice, results in increased bone resorption and decreased structural integrity of the bone, leading to a reduction in trabecular bone volume at 32 weeks of age. These data provide evidence of a role for androgens in the maintenance of trabecular bone volume directly through DNA binding,dependent actions of the AR in mature osteoblasts. [source] ,3 -Adrenoceptors in urinary bladder,,NEUROUROLOGY AND URODYNAMICS, Issue 6 2007Osamu Yamaguchi Abstract The ,-adrenoceptor (AR) is currently classified into ,1, ,2, and ,3 subtypes. A third subtype, ,3 -AR, was first identified in adipose tissue, but has also been identified in smooth muscle tissue, particularly in the gastrointestinal tract and urinary bladder smooth muscle. There is a predominant expression of ,3 -AR messenger RNA (mRNA) in human bladder, with 97% of total ,-AR mRNA being represented by the ,3 -AR subtype and only 1.5 and 1.4% by the ,1 -AR and , 2 -AR subtypes, respectively. Moreover, the presence of ,1 -, ,2 -, and ,3 -AR mRNAs in the urothelium of human bladder has been identified. The distribution of ,-AR subtypes mediating detrusor muscle relaxation is species dependent, the predominant subtype being the ,3 -AR in humans. Recent studies have suggested that cAMP-dependent routes are not exclusive mechanisms triggering the ,-AR-mediated relaxation of smooth muscle. It has been demonstrated in rats detrusor muscle that cAMP plays a greater role in ,-adrenergic relaxation against basal tone than against KCl-induced tone and that conversely calcium-activated K+ channels (BKca channels) play a greater role under the latter circumstances. In rat models, ,3 -AR agonists increase bladder capacity without influencing bladder contraction and have only weak cardiovascular side effects. Although this evidence points toward the clinical utility of ,3 -AR agonists as therapy for overactive bladder (OAB), pharmacological differences exist between rat and human ,3 -ARs. Development of compounds with high selectivity for the human ,3 -AR, identified by screening techniques using cell lines transfected with the human ,1 -, ,2 -, and ,3 -AR genes, may mitigate against such problems. The association between the tryptophan 64 arginine polymorphism in the ,3 -AR gene and idiopathic OAB is discussed. Neurourol. Urodynam. 26:752,756, 2007. © 2007 Wiley-Liss, Inc. [source] An unexpected wide population variation of the G1733A polymorphism of the androgen receptor gene: Data on the Mediterranean regionAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 6 2005E. Esteban The androgen receptor (AR) has been proposed as a candidate gene for several cancers (breast, prostate, uterine endometrium, colon, and esophagus). Ethnicity is considered an associated risk factor for some of these cancers. Several case-control genetic studies have been focused in samples of the main ethnic groups, but little is known about the distribution of risk polymorphisms in current populations with accurate ethnic and/or geographic origins. The A allele of the G1733A polymorphism of the AR gene has been associated with increased risk of prostate cancer. We provide data from this marker in 12 samples from 7 Mediterranean countries such as Spain, Italy (Sardinia), Greece, Turkey, Morocco, Algeria, and Egypt. A sample from Ivory Coast has also been analyzed. The A allele distribution shows a frequency in the Ivory Coast population (65.17%) that contrasts with the low values found in Northern Mediterraneans (mean average value of 13.98%). North African populations present two-times higher frequencies (average value of 27.19%) than Europeans. The wide population variation range found for the A allele strengthens the potential interest of further screening as a baseline to the design of future preventive and population health programs. Am. J. Hum. Biol. 17:690,695, 2005. © 2005 Wiley-Liss, Inc. [source] Mutation screening of the androgen receptor promoter and untranslated regions in prostate cancerTHE PROSTATE, Issue 15 2006Kati K. Waltering Abstract Background Mechanisms, other than gene amplification, leading to overexpression of AR in androgen ablation-resistant prostate cancer remain unknown and could include genetic alterations in the promoter or untranslated regions (UTR) of the AR gene. Materials and Methods DNAs from five prostate cancer cell lines, 19 LuCaP xenografts, 44 clinical tumors, and 36 non-malignant controls were used for screening mutations in the upstream regulatory region, promoter and the 5,- and 3,-UTRs of the AR gene with denaturating high performance liquid chromatography (DHPLC) and sequencing. Results Ten different sequence variations were found in prostate cancer cell lines and xenografts. However, none of them were recurrent or were found in clinical prostate cancer specimens or in normal controls. Conclusions Recurrent mutations in the promoter or UTRs of AR seem to be rare, and thus not likely mechanisms for the increased expression of the gene in the androgen ablation-resistant prostate cancer. Prostate 66: 1585,1591, 2006. © 2006 Wiley-Liss, Inc. [source] Parent,Daughter Transmission of the Androgen Receptor Gene as an Explanation of the Effect of Father Absence on Age of MenarcheCHILD DEVELOPMENT, Issue 4 2002David E. Comings Based on an evolutionary theory of socialization, Belsky and colleagues proposed that girls exposed to a stressful environment, especially when due to father absence in the first 7 years of life, showed an early onset of puberty, precocious sexuality, and unstable relationships as adults. The authors of this article examined an alternative explanation that a variant X,linked androgen receptor (AR) gene, predisposing the father to behaviors that include family abandonment, may be passed to their daughters causing early puberty, precocious sexuality, and behavior problems. The results of a study of 121 White males and 164 White females showed a significant association of the short alleles of the GGC repeat polymorphism of the AR gene with a range of measures of aggression and impulsivity, increased number of sexual partners, sexual compulsivity, and lifetime number of sex partners in males; and paternal divorce, father absence, and early age of menarche in females. These findings support a genetic explanation of the Belsky psychosocial evolutionary hypothesis regarding the association of fathers' absence and parental stress with early age of onset of menarche and early sexual activity in their daughters. A genetic explanation of the father absence effect is proposed in which fathers carrying the AR alleles are more likely to abandon a marriage (father absence) and pass those alleles to their daughters in whom they produce an earlier age of menarche and behavioral problems. [source] Autosomal Recessive Idiopathic Epilepsy in an Inbred Family from Turkey: Identification of a Putative Locus on Chromosome 9q32-33EPILEPSIA, Issue 5 2004Betül Baykan Summary: Purpose: The study describes the clinical features of an inbred family from Turkey with three members affected by seizures and tests possible autosomal recessive (AR) inheritance by means of linkage analysis. Methods: Personal and family history was obtained from each subject, and general physical, neurologic, and EEG examinations were performed. A set of 382 fluorescence-labeled markers was used for the initial genome-wide search. A further set of 83 markers was used to map the locus precisely and to exclude the remaining genome. Results: Twelve individuals from three generations were examined. Two subjects were affected by idiopathic epilepsy, whereas, their brother experienced a single unprovoked generalized seizure. Two siblings affected by idiopathic epilepsy and their unaffected sister showed a photoparoxysmal response to photic stimulation. Nine family members reported migraine. The genome-wide search led to the identification of a unique homozygous, 15.1-cM region shared by subjects with seizures on chromosome 9q32-33 and providing a lod score of 2.9. This locus, however, was not associated with migraine in this pedigree. Conclusions: The study suggests that idiopathic epileptic traits with AR inheritance might be underestimated in the general population and that inbred pedigrees may represent powerful tools for the identification of AR genes. [source] ,3 -Adrenoceptors in urinary bladder,,NEUROUROLOGY AND URODYNAMICS, Issue 6 2007Osamu Yamaguchi Abstract The ,-adrenoceptor (AR) is currently classified into ,1, ,2, and ,3 subtypes. A third subtype, ,3 -AR, was first identified in adipose tissue, but has also been identified in smooth muscle tissue, particularly in the gastrointestinal tract and urinary bladder smooth muscle. There is a predominant expression of ,3 -AR messenger RNA (mRNA) in human bladder, with 97% of total ,-AR mRNA being represented by the ,3 -AR subtype and only 1.5 and 1.4% by the ,1 -AR and , 2 -AR subtypes, respectively. Moreover, the presence of ,1 -, ,2 -, and ,3 -AR mRNAs in the urothelium of human bladder has been identified. The distribution of ,-AR subtypes mediating detrusor muscle relaxation is species dependent, the predominant subtype being the ,3 -AR in humans. Recent studies have suggested that cAMP-dependent routes are not exclusive mechanisms triggering the ,-AR-mediated relaxation of smooth muscle. It has been demonstrated in rats detrusor muscle that cAMP plays a greater role in ,-adrenergic relaxation against basal tone than against KCl-induced tone and that conversely calcium-activated K+ channels (BKca channels) play a greater role under the latter circumstances. In rat models, ,3 -AR agonists increase bladder capacity without influencing bladder contraction and have only weak cardiovascular side effects. Although this evidence points toward the clinical utility of ,3 -AR agonists as therapy for overactive bladder (OAB), pharmacological differences exist between rat and human ,3 -ARs. Development of compounds with high selectivity for the human ,3 -AR, identified by screening techniques using cell lines transfected with the human ,1 -, ,2 -, and ,3 -AR genes, may mitigate against such problems. The association between the tryptophan 64 arginine polymorphism in the ,3 -AR gene and idiopathic OAB is discussed. Neurourol. Urodynam. 26:752,756, 2007. © 2007 Wiley-Liss, Inc. [source] Distribution of genotypes and antibiotic resistance genes among invasive Streptococcus agalactiae (group B streptococcus) isolates from Australasian patients belonging to different age groupsCLINICAL MICROBIOLOGY AND INFECTION, Issue 3 2008Z. Zhao Abstract Serotype distribution and antibiotic resistance (AR) among group B streptococci (GBS) affect GBS disease prevention strategies, but vary among patient groups. A multiplex PCR-based reverse line blot (mPCR/RLB) hybridisation assay was used to compare the distributions of GBS serotypes, serotype III subtypes and AR-associated genes among 666 invasive isolates from 663 patients, divided into five age groups: infants, early-onset (EO; 0,6 days) and late-onset (LO; 7,90 days); children (aged 3 months to 14 years); women of childbearing age (WCBA; aged 15,45 years); and other adults (males aged >15 years; females aged >45 years). Serotypes Ia and V and serosubtype III-1 accounted for 60% of infections. Serosubtype III-2, which corresponds to a virulent clone belonging to sequence type (ST)17, was relatively uncommon overall (7%), but was associated strongly with LO infant infections, in which it was significantly more common than in adult infections (25/104 (24%) vs. 9/392 (2%), p <0.0001) or in EO infections (25/104 (24%) vs. 14/155 (9%), p <0.005). Erythromycin resistance genes were found in 8% of all isolates (ermB 3%, ermA 2.5% and mefA/E 2%), in 11,15% of isolates of serotypes II and V and subtype III-1, but in none of the isolates of serosubtype III-2 (III-2, 0/49 vs. all others, 54/618 (9%), p <0.04). In summary, the virulent serosubtype III-2 was associated strongly with LO infant GBS infection, but was less likely than other serotypes or serosubtype III-1 to carry AR genes. [source] Androgen receptor gene expression in the developing and adult zebrafish brainDEVELOPMENTAL DYNAMICS, Issue 10 2008Daniel A. Gorelick Abstract Androgens play a central role in the regulation of male sexual differentiation and behavior in many vertebrates, including zebrafish. Their signaling is mediated by activation of the androgen receptor. A single androgen receptor (ar) gene was recently identified in zebrafish, which encodes a protein that binds androgens in vitro. However, the tissue-specific expression pattern of this receptor in vivo has not been described. Using whole-mount RNA in situ hybridization, we characterized expression of the ar gene in developing zebrafish and in the adult brain. In embryos, transcripts were found in the presumptive pronephros and in olfactory placodes. By 3,5 days postfertilization, ar transcripts were also detected in the pineal organ anlage and the retina. In the adult brain, ar was expressed in discrete regions of the telencephalon, in the preoptic area, and throughout the periventricular hypothalamus, regions previously implicated in the regulation of sexually dimorphic behaviors in mammals. Developmental Dynamics 237:2987,2995, 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||