Dataset Information

Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia.

ABSTRACT: Dutasteride, a dual inhibitor of both type I and II 5?-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher's exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models.

SUBMITTER: Rhie A

PROVIDER: S-EPMC6746394 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia.

Rhie Arang A Son Ho-Young HY Kwak Soo Jung SJ Lee Seungbok S Kim Dong Young DY Lew Bark-Lynn BL Sim Woo-Young WY Seo Jeong-Sun JS Kwon Ohsang O Kim Jong-Il JI Jo Seong Jin SJ

PloS one 20190916 9

Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, a ...[more]

PMID: 31525235

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Project description:BackgroundEarly-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA.MethodsElectronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary.ResultsAmong the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss.ConclusionEarly-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.

Project description:BackgroundAlthough androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear.MethodsThe microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells.ResultsThe ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response.ConclusionIn summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

Dataset Information

Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia.

Publications

Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia.

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