Background: CAG repeat length in exon 1 of the androgen receptor (AR) gene correlates inversely with transcriptional transactivation activity of the AR. Men with shorter AR CAG repeat lengths are at higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that a shorter AR gene CAG repeat length increases the risk of developing of BPH.
Methods: Among 14,916 men of the Physicians' Health Study who had provided a blood sample in 1982, we measured AR gene CAG repeat lengths for 310 men who had surgery for BPH up to 7.5 years of follow-up and 1,041 controls.
Results: Risk of surgery for BPH increased linearly with decreasing AR CAG repeat length (P (trend) = 0.03). Relative to men with a CAG repeat length > or = 25, men with a repeat length < or = 19 had an odds ratio of BPH surgery of 1.76 (95% confidence interval, 1.16-2.65).
Conclusions: Variability in the AR gene CAG repeat influences the development of symptomatic BPH.
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http://dx.doi.org/10.1002/(sici)1097-0045(19990501)39:2<130::aid-pros8>3.0.co;2-# | DOI Listing |
Huntington's Disease (HD), a progressive neurodegenerative disorder with no disease-modifying therapies, is caused by a CAG repeat expansion in the HD gene encoding polyglutamine-expanded huntingtin (HTT) protein. Mechanisms of HD cellular pathogenesis and cellular functions of the normal and mutant HTT proteins are still not completely understood. HTT protein has numerous interaction partners, and it likely provides a scaffold for assembly of multiprotein complexes many of which may be altered in HD.
View Article and Find Full Text PDFNat Neurosci
January 2025
Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA.
Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.
View Article and Find Full Text PDFEur J Neurol
January 2025
Institut du Cerveau-Paris Brain Institute ICM, Sorbonne Université, Inserm 1127, CNRS 7225, Hôpital de la Pitié Salpêtrière Paris, Paris, France.
Objective: Spinocerebellar ataxias (SCA) are neurodegenerative diseases with widespread lesions across the central nervous system. Ataxia and spasticity are usually predominant, but patients may also present with parkinsonism. We aimed to characterize substantia nigra pars compacta (SNc) degeneration in SCA2 and 7 using neuromelanin-sensitive imaging.
View Article and Find Full Text PDFStem Cell Res
December 2024
Emergency and Critical Care Department, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao 266042, China. Electronic address:
A human induced pluripotent stem cell (iPSC) line was generated from patient with Kennedy Disease (KD), who carried the CAG repeat expansion mutation in AR gene. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating delivery of KFL4, OCT4, SOX2, BCL-XL and c-MYC. The iPSC line expresses pluripotency markers, displays a normal karyotype, and is capable of differentiate into three germ layers in vitro.
View Article and Find Full Text PDFNeurocase
January 2025
Department of Neurology, Dongguk University College of Medicine, Dongguk University Gyeongju Hospital, Gyeongju, Republic of Korea.
Dentatorubral-Pallidoluysian Atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the ATN1 gene, characterized by diverse neurological and psychiatric symptoms. We report a 23-year-old patient with juvenile-onset seizures, cognitive decline, and ataxia, progressing to psychosis by age 31. Initial brain MRI showed minimal cerebellar atrophy, with prominent atrophy evident on follow-up imaging.
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