Genome-wide scan and fine-mapping linkage study of androgenetic alopecia reveals a locus on chromosome 3q26.
ABSTRACT: Androgenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample of 125 families of German descent. The locus with strongest evidence for linkage was mapped to 3q26 with a nonparametric linkage (NPL) score of 3.97 (empirical p value = 0.00055). This is the first step toward the identification of new susceptibility genes in AGA, a process which will provide important insights into the molecular and cellular basis of scalp hair loss.
Project description:Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.
Project description:The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®.
Project description:Platelet-rich plasma (PRP) treatment has gained popularity among different surgical specialities for improving various conditions. Androgenetic alopecia (AGA) is a common disorder, with possible psychosocial implications. Plastic surgeons have increased the practice of PRP injections for hair restoration. A meta-analysis on this topic was performed comparing local injection of PRP versus control to investigate the efficacy of local PRP injections in AGA.We performed a systematic literature search. The increase in number of hairs was the primary outcome. Secondary outcomes were the increase of hair thickness and the percentage increase in hair number and thickness.Seven studies involving 194 patients were retrieved and included in the present analysis. A significantly locally increased hair number per cm2 was observed after PRP injections versus control (mean difference [MD] 14.38, 95% confidence interval [CI] 6.38-22.38, P < 0.001). Similarly, a significantly increased hair thickness cross-section per 10-4 mm2 (MD 0.22, 95% CI 0.07-0.38, P = 0.005) favoring PRP group. The pooled results did not show a significant percentage increase in hair number (MD 18.79%, 95% CI - 8.50-46.08, P = 0.18), neither hair thickness (MD 32.63%, 95% CI - 16.23-81.48, P = 0.19) among patients treated with PRP.Local injection of PRP for androgenic alopecia might be associated with an increased number of hairs in the treated areas with minimal morbidity, but there is clearly a lack of scientific evidence on this treatment modality. Further studies are needed to evaluate the efficacy of PRP for AGA.
Project description:Accumulating evidence suggests that adipose-derived stem cell constituent extract (ADSC-CE) helps hair regrowth in patients with androgenetic alopecia (AGA). However, the effects of ADSC-CE have not been demonstrated in a randomized, double-blind, vehicle-controlled clinical trial. In this randomized, double-blind, vehicle-controlled clinical trial, 38 patients (29 men) with AGA were assigned to an intervention group (IG), with twice-daily self-application of the ADSC-CE topical solution over the scalp with fingers, or to a control group (CG). Changes in hair count and thickness at 16?weeks from the baseline were evaluated using a phototrichogram. Overall, 34 (89%) patients (mean age, 45.3?years) completed the study. The phototrichogram at week 8 showed more increase in hair count in the IG than in the CG, and intergroup differences in the change of hair count remained significant until week 16 with overall changes of 28.1% vs 7.1%, respectively. Similarly, a significant improvement in hair diameter was observed in the IG (14.2%) after 16?weeks when compared with hair diameter in the CG (6.3%). Our findings suggest that the application of the ADSC-CE topical solution has enormous potential as an alternative therapeutic strategy for hair regrowth in patients with AGA, by increasing both hair density and thickness while maintaining adequate treatment safety.
Project description:BACKGROUND: Androgenetic alopecia (AGA) is a well-characterized type of progressive hair loss commonly seen in men, with different prevalences in different ethnic populations. It is generally considered to be a polygenic heritable trait. Several susceptibility genes/loci, such as AR/EDA2R, HDAC9 and 20p11, have been identified as being involved in its development in European populations. In this study, we aim to validate whether these loci are also associated with AGA in the Chinese Han population. METHODS: We genotyped 16 previously reported single nucleotide polymorphisms (SNPs) with 445 AGA cases and 546 healthy controls using the Sequenom iPlex platform. The trend test was used to evaluate the association between these loci and AGA in the Chinese Han population. Conservatively accounting for multiple testing by the Bonferroni correction, the threshold for statistical significance was P ? 3.13 × 10(-3). RESULTS: We identified that 5 SNPs at 20p11 were significantly associated with AGA in the Chinese Han population (1.84 × 10(-11) ? P ? 2.10 × 10(-6)). CONCLUSIONS: This study validated, for the first time, that 20p11 also confers risk for AGA in the Chinese Han population and implicated the potential common genetic factors for AGA shared by both Chinese and European populations.
Project description:Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, ?6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.
Project description:BACKGROUND:There are regional variations in the scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions have been less well studied. OBJECTIVES:To determine whether scalp biopsies from men with AGA show variable gene expression before and after 8 weeks of treatment with minoxidil topical foam 5% (MTF) vs. placebo. METHODS:A placebo-controlled double-blinded prospective pilot study of MTF vs. placebo was conducted in 16 healthy men aged 18-49 years with Hamilton-Norwood type IV-V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for 8 weeks. Stereotactic scalp photographs were taken at the baseline and final visits, to monitor global hair growth. Scalp biopsies were taken at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo, and microarray analysis was performed using the Affymetrix GeneChip HG U133 Plus 2.0. RESULTS:Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of patients with AGA. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin-associated genes and decreased the expression of epidermal differentiation complex and inflammatory genes in both scalp regions. CONCLUSIONS:These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of patients with AGA.
Project description:Background:Androgenetic alopecia (AGA) is the most common cause of hair loss in men with limited treatment options. Platelet-rich plasma (PRP) therapy is one of the newer treatment options in the management of AGA which has shown promising results. Aims and Objectives:This study was aimed at comparing the clinical efficacy of PRP therapy with minoxidil therapy. Materials and Methods:In the study, patients were randomized into two groups - Group A (given PRP therapy) and Group B (given minoxidil therapy). Both groups were followed up over a period of 6 months, and final analysis was done with the help of global photography, hair pull test, standardized hair growth questionnaire, patient satisfaction score; in addition, a comparison of platelet counts in PRP was done, to know that if a clinical correlation exists between platelet concentration and clinical improvement. A total of 40 patients clinically diagnosed with AGA were enrolled in the study with 20 patients in each group. Four patients from Group A (PRP) and six patients from Group B (minoxidil) could not complete the treatment for 6 months and were eventually excluded. Results:At the end of 6 months, 30 patients were evaluated to compare the efficacy of intradermal PRP and topical minoxidil therapy. On global photography, Group A (PRP) was found to have a comparatively better outcome than Group B (minoxidil). In hair pull test, hair growth questionnaire, and patient satisfaction score, Group A was found to be better than Group B. Mean platelet count at baseline was 3.07 ± 0.5 lac/mm, 3 while platelet count in final PRP prepared was 12.4 ± 1.7 lac/mm, and patients with a higher platelet count in PRP had a much better clinical improvement compared to patients with a low platelet count in PRP. Side effects with PRP therapy were minimal with better results which may improve the compliance of the patient. Conclusion:PRP therapy can be a valuable alternative to topical minoxidil therapy in the treatment of AGA.
Project description:To fully interrogate location-specific variations of the hair follicle in AGA and normal persons, we sought to perform a thorough and comprehensive transcripotome profiling of different locations of hair follicles (bulb portions, bulge portions) in balding and non-balding areas of AGA, with normal comparisons. Overall design: Hair follicles harvested by follicular unit extraction came respectively from vertex (balding) and occipital (nonbalding) areas from 12 patients and occipital areas from 12 control subjects. Using microdissection, hair follicle was separated into two parts(bulb and bulge portion) for further study.
Project description:Androgenetic alopecia (AGA), or male-pattern baldness, is the most common form of hair loss. Its pathogenesis is androgen dependent, and genetic predisposition is the major requirement for the phenotype. We demonstrate that genetic variability in the androgen receptor gene (AR) is the cardinal prerequisite for the development of early-onset AGA, with an etiological fraction of 0.46. The investigation of a large number of genetic variants covering the AR locus suggests that a polyglycine-encoding GGN repeat in exon 1 is a plausible candidate for conferring the functional effect. The X-chromosomal location of AR stresses the importance of the maternal line in the inheritance of AGA.