Risk Of Androgenetic Alopecia Research Articles

The Role of rs6152 Allele and Non-Genetic Factors in Androgenetic Alopecia: A Pilot Study in the Indonesian Local Population

Background: Androgenetic alopecia (AGA) is a common form of hair loss which inflicts progressive hair loss leading to various patterns. The cause of this disease is believed to be multifactorial, which is majorly attributed to genetic and non-genetic factors. This pilot study aimed to investigate the association of rs6152 allele, a SNP on AR gene, with AGA, as well as explore other contributing factors in the Indonesian local population.
 Methods: In this cross-sectional study, a total of 100 participants, which categorized into alopecia subjects and non-alopecia subjects, were enrolled for rs6152 SNPs detection. Anthropomorphic data such as height and weight, blood pressure and family history were obtained by measurement and questionnaire.
 Results: The study showed low frequency of individuals with rs6152 non-risk alleles (2%) and further analysis showed no significant association between rs6152 allele and AGA. However, familial history analysis revealed a strong association between family history and AGA risks. Additionally, age, gender, hypertension status and BMI were identified as significant factors associated (p-value < 0.05) with AGA.
 Conclusion: rs6152 was not a reliable genetic marker for AGA in the Indonesian local population. While familial history with AGA showed the inheritance pattern of autosomal dominant inheritance with sex limitation, non-genetic factors such as age, gender, hypertension status and BMI were strongly associated with AGA risk. This shows the complexity and multifactorial causes of AGA in the Indonesian local population.

Bioinformatic analysis of gene expression data reveals Src family protein tyrosine kinases as key players in androgenetic alopecia.

Androgenetic alopecia (AGA) is a common progressive scalp hair loss disorder that leads to baldness. This study aimed to identify core genes and pathways involved in premature AGA through an in-silico approach. Gene expression data (GSE90594) from vertex scalps of men with premature AGA and men without pattern hair loss was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the bald and haired samples were identified using the limma package in R. Gene ontology and Reactome pathway enrichment analyses were conducted separately for the up-regulated and down-regulated genes. The DEGs were annotated with the AGA risk loci, and motif analysis in the promoters of the DEGs was also carried out. STRING Protein-protein interaction (PPI) and Reactome Functional Interaction (FI) networks were constructed using the DEGs, and the networks were analyzed to identify hub genes that play could play crucial roles in AGA pathogenesis. The in-silico study revealed that genes involved in the structural makeup of the skin epidermis, hair follicle development, and hair cycle are down-regulated, while genes associated with the innate and adaptive immune systems, cytokine signaling, and interferon signaling pathways are up-regulated in the balding scalps of AGA. The PPI and FI network analyses identified 25 hub genes namely CTNNB1, EGF, GNAI3, NRAS, BTK, ESR1, HCK, ITGB7, LCK, LCP2, LYN, PDGFRB, PIK3CD, PTPN6, RAC2, SPI1, STAT3, STAT5A, VAV1, PSMB8, HLA-A, HLA-F, HLA-E, IRF4, and ITGAM that play crucial roles in AGA pathogenesis. The study also implicates that Src family tyrosine kinase genes such as LCK, and LYN in the up-regulation of the inflammatory process in the balding scalps of AGA highlighting their potential as therapeutic targets for future investigations.

Second-to-fourth digit ratio and age predicting the severity of androgenetic alopecia: a cross-sectional study

Purpose: Androgenetic alopecia (AGA) is a common type of hair loss. Previous studies indicated that the relative length of the index and ring finger (2D:4D ratio) of AGA patients was lower than control. However, the correlation between 2D:4D ratio and disease severity is unclear. In this study, we sought to evaluate the relationship between digit ratio of the right hand and AGA severity in male patients. Materials and methods: The cross-sectional study was performed. Hamilton–Norwood scale was used to assess severity. The finger lengths of the right hand were measured using a digital caliper. Results: Our study found that the lower the right-handed 2D:4D ratio, the greater the risk of developing AGA and that the severity of AGA increases with age. Patients with moderate and severe AGA (grade 3 and above) had lower 2D:4D ratios and higher average age compared with patients with mild AGA (Norwood grade 2). Patients aged ≥37.5 with a 2D:4D ratio <0.947 were six times more likely to have moderate-to-severe androgenetic alopecia compared with the reference group (OR: 6.11; 95% CI: 1.96–19.04). Conclusions: Combining 2D:4D ratio and older age may help predict the severity risk of AGA, and offer a clinically accessible, non-invasive approach for patients to easily predict their future severity.

The first broad replication study of SNPs and a pilot genome-wide association study for androgenetic alopecia in Asian populations.

Many candidate genes for androgenetic alopecia (AGA) have been identified in studies of the Caucasians and some Asian populations. This study aimed to confirm the known susceptibility genes reported in previous studies and find additional candidate genes for high-risk individuals for AGA in Korean population. We recapitulated the previously reported SNPs and identified the novel Korean AGA risk genetic variants using a Korean hospital-based AGA case and control samples. The population was consisting of 494 individuals (275 AGA cases and 146 controls). Using the 800 K SNPs of precision medical research array (PMRA SNP microarray chip) and imputation-based SNPs, 12 previous GWAS reports for AGA and a total of 62 160 SNPs were examined in our study samples. Also, we conducted the genome-wide association study (GWAS) by the logistic regression analyses for AGA cases and controls with controlling the age as the covariates. Among the 62 160 SNPs, a total of 1143 SNPs in 76 gene regions showed weak replication tendency with the p-values <0.05 and same direction of effects. Additionally, the GWAS results showed 110 SNPs in 13 independent regions with the suggestive p-values <1.00 × 10-5 . The most significantly replicated SNP resided on chromosome 20, which were similar to other AGA replication studies including Chinese study. The GWAS identified two SNPs (rs11010734 and rs2420640) increasing the risk for AGA in our study population. Our study would be a reference of the non-European studies to better understand AGA in different populations and ancestral contexts.

Epidemiology and disease burden of androgenetic alopecia in college freshmen in China: A population-based study.

ObjectiveTo evaluate the epidemiology and disease burden of androgenetic alopecia (AGA) in college freshmen in China.MethodsThis population-based cross-sectional survey was carried out among 9227 freshmen of two comprehensive universities in two cities of China (Changsha and Xiamen) from September 2018 to October 2018. Questionnaires covering basic issues, surrounding demographic information, history of diseases, living habits, comorbidities, etc. were completed online in a self-reported manner Dermatological examination was performed by certified dermatologists. The disease burden of AGA, which includes health-related quality of life, symptoms of anxiety, symptoms of depression and quality of sleep, was measured by EQ-5D-3L, PHQ-2, GAD-2 and PSQI, respectively.ResultsThe prevalence of AGA in college freshmen in China was 5.3/1000. Male was significantly associated with higher prevalence of AGA (7.9/1000, P<0.01) while female with lower risk of AGA (OR = 0.29, P = 0.002). There was no significant association between BMI and AGA, nor predilection of AGA in the Han nationality or the other ethnic minorities. Annual household income or parental highest educational level exerted no significant influence on the prevalence of AGA. Rosacea (OR = 3.22, P = 0.019) was significantly associated with higher prevalence of AGA while acne seemed not to be related to AGA. The scores of EQ-5D, GAD-2, PHQ-2 and PSQI were not significantly different between students with and without AGA.ConclusionThe onset of AGA in Chinese college freshmen differ between genders and was significantly associated with rosacea.

Mediterranean diet: fresh herbs and fresh vegetables decrease the risk of Androgenetic Alopecia in males.

It is well established that Androgenetic Alopecia (AGA) occurs in genetically predisposed individuals but little is known of its non-genetic risk factors. The aim of the study was to investigate the role of the Mediterranean diet in determining the risk of AGA. A hospital-based case-control study was conducted in the outpatient clinics of the hospital "Istituto Dermopatico dell'Immacolata, Rome, Italy". We included 104 males and 108 controls not affected by AGA. Controls were frequency matched to cases. Information on socio-demographic characteristics, medical history, smoking and diet were collected for all patients. Logistic regression was used to estimate odds ratio and 95% confidence intervals. After controlling for age, education, body mass index and family history of AGA, protective effects for AGA were found for high consumption (≥ 3 times weekly) of raw vegetables (OR 0.43; 95% CI 0.21-0.89) and high consumption of fresh herbs (3 or more regularly) (OR 0.44; 95% CI 0.22-0.87). We suggest that some foods of the Mediterranean diet, say fresh herbs and salad, may reduce the risk of AGA onset.

Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Androgenetic alopecia (AGA) is a common heritable and androgen-dependent hair loss condition in men. Twelve genetic risk loci are known to date, but it is unclear which genes at these loci are relevant for AGA. Dermal papilla cells (DPCs) located in the hair bulb are the main site of androgen activity in the hair follicle. Widely used monolayer-cultured primary DPCs in hair-related studies often lack dermal papilla characteristics. In contrast, immortalized DPCs have high resemblance to intact dermal papilla. We derived immortalized human DPC lines from balding (BAB) and non-balding (BAN) scalp. Both BAB and BAN retained high proportions of dermal papilla signature gene and versican protein expression. We performed expression analysis of BAB and BAN and annotated AGA risk loci with differentially expressed genes. We found evidence for AR but not EDA2R as the candidate gene at the AGA risk locus on chromosome X. Further, our data suggest TWIST1 (twist family basic helix-loop-helix transcription factor 1) and SSPN (sarcospan) to be the functionally relevant AGA genes at the 7p21.1 and 12p12.1 risk loci, respectively. Down-regulated genes in BAB compared to BAN were highly enriched for vasculature-related genes, suggesting that deficiency of DPC from balding scalps in fostering vascularization around the hair follicle may contribute to the development of AGA.

Inflammatory markers and Lp(a) levels as cardiovascular risk factors in androgenetic alopecia.

It is not well-established whether patients with androgenetic alopecia (AGA) show a higher cardiovascular risk and higher prevalence of metabolic syndrome (MS). Therefore, we aimed to analyze the cardiovascular risk and the prevalence of MS by means of a case-control study. We determined lipidic, inflammatory, hormonal and insulin resistance parameters with conventional laboratory methods in 50 male early-onset AGA patients and 50 controls. AGA patients did not show statistical differences for insulin resistance (glucose, insulin, C peptide, HOMA), lipids (total-cholesterol, HDL-cholesterol, tryglicerides) or hormonal parameters (testosterone, free androgen index, sex hormone-binding globulin) P >  0.05, respectively. No differences between groups were observed in prevalence of MS or its components (P >  0.05). AGA patients showed higher levels of fibrinogen, C-reactive protein (CRP) and lipoprotein(a) (Lp(a)) (P = 0.016, P = 0.019 and P = 0.032, respectively). In the unadjusted logistic regression analyses, PCR >4 mg/L, fibrinogen >395 mg/dL and Lp(a) >59 mg/dL increased the risk of AGA, but in the adjusted logistic regression analyses, only PCR >4 mg/L and Lp(a) >59 mg/dL independently increased this risk (OR = 5.83, 95% CI 1.33-25.59 P = 0.020; OR = 3.94 CI 95% 1.08-14.43 P = 0.038). The present study indicates that AGA patients do not show differences in either insulin resistance or prevalence of MS. However, AGA patients show a higher cardiovascular risk characterised by an increase in inflammatory parameters and Lp(a) levels.

Investigation of four novel male androgenetic alopecia susceptibility loci: no association with female pattern hair loss

Female pattern hair loss (FPHL) is a common hair loss disorder in women and has a complex mode of inheritance. The etiopathogenesis of FPHL is largely unknown; however, it is hypothesized that FPHL and male pattern baldness [androgenetic alopecia (AGA)] share common genetic susceptibility alleles. Our recent findings indicate that the major AGA locus, an X-chromosome region containing the androgen receptor and the ectodysplasin A2 receptor (EDA2R) genes, may represent a common genetic factor underlying both early-onset FPHL and AGA. This gives further support for the widespread assumption of shared susceptibility loci for FPHL and AGA. However, we could not demonstrate association of further AGA risk loci, including 20p11, 1p36.22, 2q37.3, 7p21.1, 7q11.22, 17q21.31, and 18q21.1, with FPHL. Interestingly, a recent study identified four novel AGA risk loci in chromosomal regions 2q35, 3q25.1, 5q33.3, and 12p12.1. In particular, the 2q35 locus and its gene WNT10A point to an as-yet unknown involvement of the WNT signaling pathway in AGA. We hypothesized that the novel loci and thus also the WNT signaling may have a role in the etiopathogenesis of FPHL and therefore examined the role of these novel AGA risk loci in our FPHL samples comprising 440 German and 145 UK affected patients, 500 German unselected controls (blood donors), and 179 UK supercontrols. Patients and controls were genotyped for the top two single nucleotide polymorphisms at each of the four AGA loci. However, none of the genotyped variants displayed any significant association. In conclusion, the results of this study provide no support for the hypothesis that the novel AGA loci influence susceptibility to FPHL.

Genetic analysis of 5 α reductase type 2 enzyme in relation to oxidative stress in cases of androgenetic alopecia in a sample of egyptian population

Objective: To study the genetic polymorphism of 5-α reductase type II enzyme in relation to oxidative stress in cases of androgenetic alopecia (AGA) in a sample of Egyptian population. Materials and Methods: This study was conducted on 45 patients with different grades of AGA,and 45 healthy subjects as control group. Laboratory tests included DNA extraction from blood, amplification of the 5-α reductase type II by PCR and V89L mutation analysis by restriction endonuclease enzyme RsaІ, and estimation of the levels of plasma catalase and erythrocyte lysate superoxide dismutase (SOD) enzymes by colorimetric methods. Results: The studied subjects carrying the homozygote( LL) and the heterozygote (VL) genotypes were of no risk of developing AGA.(OR=0). Regarding the leucine allele, the studied subjects carrying the (L) allele were at about 3.7 higher risk of AGA .(OR=3.692), and the results were statistically significant (p<0.001). There was significant increase in the level of SOD and catalase in patients than in control group(p=0.005),and (p<0.001) respectively,plasma catalase is significantly higher in patients with LLvariant than inVL variant (p=0.020). Asignificant relations was found between the severity of the disease and age and family history (p=0.037), and (0.036) respectively, there was no significant correlation between the level of catalase enzyme and SOD in one hand and the severity of the disease among patients. Conclusions: There is a possible association between AGA and V89L genetic polymorphism of 5-alpha reductase type II enzyme, patients carrying the mutant leucine (L) allele have a risk for developing AGA. Also there is possible association between AGA with oxidative stress.

Androgenetic alopecia in policemen: higher prevalence and different risk factors relative to the general population (KCIS no. 23)

Prevalence and risk factors of androgenetic alopecia (AGA) in policemen are not known. This study aimed to compare the prevalence and risk factors of AGA between policemen and the general population. A cross-sectional survey was conducted by recruiting a total of 758 (78%) of 972 policemen and 740 (80%) of 924 participants in a community-based integrated screening served as a comparison group. The Norwood classification system was used to assess the degree of hair loss. Information on age, family history of androgenetic alopecia, and other possible risk factors was collected with questionnaire interviews. The association analysis between policemen and the general population was limited to participants aged 40-59years. After controlling for other significant factors, policemen aged 40-59years had an increased risk of developing AGA compared with the general population (OR=2.23, 95% CI 1.14, 4.36, p=0.02). Obesity measured by waist circumference and body mass index made contribution to higher risk for AGA in younger policemen (20-39years). A statistically significant association was noted between AGA and sunlight exposure in policemen aged 40-59years. We concluded the prevalence of AGA in policemen was twofold higher than that in the general population. Obesity at young age and sunlight exposure may be responsible for higher risk of AGA in policemen. However, further studies are warranted to confirm the current findings.

Quoi de neuf en recherche dermatologique ?

Medical literature is rich with new and relevant information, resulting from basic or applied research. Some strong arguments are presented in this document. Firstly, the discovery and role of a virus, the polyomavirus, in the development of Merkel tumours. It is a small virus with double bit DNA strand, coding for a oncoprotein. If the polyomavirus plays a causal role in the tumorigenesis, it acts by various mechanisms. The micro-RNAs represent an abundant class of small RNA not coding for proteins, but which control the gene expression coding for proteins on a post-transcriptional level. The first obvious sign of the role of the micro-RNAs in the inflammatory dermatoses appeared recently, in particular when these micro-RNAs associated with psoriasis and atopic dermatitis were identified through a broad genomic analysis of the expression of these micro-RNAs. A new giant virus strain sheltering another unknown tiny virus to date has just been discovered. This virus infinitely small called Sputnik enables to deteriorate a much larger virus baptized Mama, at the point of preventing it to manufacture normal viral particles and also preventing it from reproducing. This discovery raises a crucial question: Is Sputnik a new system of transfer of genes of a species of one virus to another? A group of blood cells expressing E-cadherin, the dot cells, found in the fetal blood of the dermis, contributes to tissue repair through the mechanisms of cellular differentiation and their action allows healing without scar. CD4+ T helper lymphocytes producing interleukin 17 (IL17) play a pathogenic part in atopic dermatitis. The genes of the beta defensins could be involved in the genetic susceptibility of the psoriatic disease. The autoimmune origin of the alopecia areata is supported by a great number of observations, the role of neuropeptides in the initiation of the autoimmunity during alopecia areata has just been demonstrated. The dendritic cells are cells presenting antigens which play a crucial role in the adaptive immunological response. It was shown that activation of the proliferation of the lymphocytes T after the migration of dendritic cells on the level of the lymphatic ganglion depended not on Langerhans cell, but of the dendritic cell. A new way appears to control the autoimmunity in the psoriasis and involves the plasmacytoid dendritic cells which are sensitized with the DNA itself when it is coupled with an antibacterial peptide. Mast cells express cathelicidin, which acts like an antibiotic with broad spectrum and influences the defence system of the epitheliums. We have perhaps found a new therapeutic target for rosacea by disclosing high rates of cathelicidin and a series of associated proteases in skin lesions. The sebocytes express antibacterial functional peptides deriving from cathelicidin which can have a bactericidal effect against P. Acnes. A vast genomic study in the androgenetic alopecia highlighted the existence of new loci localized on the 20p11 chromosome, associated with the risk of androgenetic alopecia. New alleles to determine the color of hair and the cutaneous pigmentation were identified. Two loci (IRF 4 and SLC24A4) are highly associated with the color of hair, like three other areas. The blue color of the eyes could be due to a change of an element located in gene HERC2 preventing of the expression of OCA2. Thus, many fields of dermatology were the object of research which opens new prospects for diagnosis and treatment.

Men with Kennedy disease have a reduced risk of androgenetic alopecia

Spinal and bulbar muscular atrophy or Kennedy disease (KD) is an X-linked neurodegenerative disease caused by an expansion of a polymorphic tandem CAG repeat within the androgen receptor (AR) gene on chromosomal locus Xq11-q12. The CAG repeat region encodes a polyglutamine tract that, when expanded to above 40 in number, results in KD, a neurodegenerative disease primarily targeting lower motor neurones. KD is also associated with partial androgen insensitivity due to loss of receptor function. Degree of expansion of this repeat region, located in the first exon, is correlated with age at onset and disease severity. Androgenetic alopecia (AGA) is a polygenic trait also associated with functional polymorphism of the AR gene. To test whether partial loss of function in the AR gene associated with CAG polymorphism reduces the risk of AGA in affected men. Members of the Kennedy's Disease Association, an American-based support group, were invited to participate in an online survey to determine the age-related prevalence of AGA among men affected by KD. Data from 115 respondents with KD were compared with data from 654 white men of European descent in Maryborough, Australia. The mean AGA score for men with KD was 1.64 (95% confidence interval, CI 1.41-1.87). The mean score for men in Maryborough was 2.82 (95% CI 2.71-2.93). The difference between the means was highly significant (P < 0.001), indicating thicker hair among the KD cohort. Treating AGA score as a continuous variable we found age to be highly significantly related to AGA score in men from Maryborough (P < 0.001) but not among men affected by KD (P = 0.90). Men with KD have a reduced risk of AGA, likely to be due to a functional alteration in the AR caused by the polyglutamine expansion.