Funding sources S.R. was a recipient of a BONFOR Gerok fellowship from the Medical Faculty of the University of Bonn. M.M.N. is recipient of a grant from the Alfried Krupp von Bohlen und Halbach‐Stiftung. R.C.B. is recipient of a Heisenberg Professorship from the German Research Foundation (DFG). This study was also funded by the British Skin Foundation (A.G.M. and R.T.‐A., 2005). Conflicts of interest: none declared. A.G.M. and R.C.B. have contributed equally to this work. Madam, Female pattern hair loss (FPHL) is a common disorder which affects around 12% of women by the age of 30 years, and 30–40% of women by the age of 70 years.1 2–3 Although its precise aetiopathogenesis is unknown, reports of familial occurrence strongly implicate genetic factors.4 5–6 Yip et al.7 recently performed a gene‐wide study of association between FPHL and the aromatase gene encoding CYP19A1, which is known to convert androgens to oestrogens in scalp hair follicles.8 They examined 61 tagging single nucleotide polymorphisms (SNPs) of CYP19A1 in an Australian sample of 484 caucasian women with grade 3–5 FPHL (according to the Sinclair scale9) and 471 controls.7 While no significant association was obtained at the allelic level, the CC genotype of rs4646 was significantly more frequent in cases (58·1%) than controls (48·9%) when compared with collapsed AC and AA groups (P =0·006), suggesting a recessive genetic effect. Although this result did not withstand experiment‐wide correction for multiple testing, its validity was supported by the following lines of evidence: (i) the highest frequency of the CC genotype (68·2%) occurred in women < 40 years, which is consistent with the hypothesis that genetic predisposition is more evident among early‐onset cases; and (ii) the rs4646 CC genotype has been associated with higher oestrogen levels than the AA genotype, which is consistent with reports that oestrogen has inhibitory effects on hair growth. Given the lack of experiment‐wide significance, the authors were cautious in their interpretation, and stressed the need for replication in independent samples. To our knowledge, the present study is the first to attempt replication of this finding.
Background The aetiology of female pattern hair loss (FPHL) is largely unknown. However, it is hypothesized that FPHL and male pattern baldness (AGA) share common susceptibility alleles. The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X‐chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified. Objectives To examine the role of the AR/EDA2R and 20p11 loci in the development of FPHL using 145 U.K. and 85 German patients with FPHL, 179 U.K. supercontrols and 150 German blood donors. Methods Patients and controls were genotyped for 25 single nucleotide polymorphisms (SNPs) at the AR/EDA2R locus and five SNPs at the 20p11 locus. Results Analysis of the AR/EDA2R locus revealed no significant association in the German sample. However, a nominally significant association for a single SNP (rs1397631) was found in the U.K. sample. Subgroup analysis of the U.K. patients revealed significant association for seven markers in patients with an early onset (P =0·047 after adjustment for the testing of multiple SNPs by Monte Carlo simulation). No significant association was obtained for the five 20p11 variants, either in the overall samples or in the analysis of subgroups. Conclusions The observed association suggests that the AR/EDA2R locus confers susceptibility to early‐onset FHPL. Our results do not implicate the 20p11 locus in the aetiology of FPHL.
Funding sources: German Research Foundation DFG, BONFOR programme of the Medical faculty of the University of Bonn. Conflicts of interest: None declared Dear Editor, The aetiopathogenesis of female pattern hair loss (FPHL) is poorly understood. Although research has strongly implicated genetic factors in familial occurrence,1 2 no association finding for FPHL has yet been replicated.3 4 5 Consequently, no causal biological pathways can be suggested on the basis of currently available genetic findings. A recent genome‐wide association study of ESR2 (oestrogen receptor 2) investigated 32 tag single‐nucleotide polymorphisms (SNPs) in an Australian FPHL sample and found nominal significance for three variants (rs10137185, rs17101774, rs2022748). The most significant SNP was rs10137185 (P = 0·003 for genotype CC versus genotypes CT + TT).6 This effect was consistent across subgroups stratified for disease severity and age‐at‐onset. Although no finding withstood experiment‐wide correction for multiple testing, the validity of the association with rs10137185 was supported by functional evidence from a public eQTL database, i.e. an association between the risk genotype CC and higher ESR2 expression levels in fibroblasts. This latter finding is consistent with reports that oestrogen has inhibitory effects on hair growth.7 In a previous study, we investigated four variants in the ESR2 gene in a U.K./German FPHL sample and found no association.5 However, this may have been attributable to the fact that none of these four variants were in strong linkage disequilibrium with variants showing association in the Australian sample (max. r2 = 0·149).
Autoimmune polyglandular syndrome type 1 (APS-1) is an inherited autosomal disorder. The most common clinical features of the disease include adrenocortical failure, hypoparathyroidism (HP), and chronic mucocutaneous candidiasis (CMC). APS-1 is caused by mutations in the autoimmune regulator (AIRE) gene. AIRE is a transcriptional factor involved in the regulation of thousands of genes in the thymus. It facilitates central tolerance by promoting the ectopic expression of tissue-specific antigens (TSAs) in medullary thymic epithelial cells (mTECs), leading to the deletion of self-reactive thymocytes. Several Aire-deficient mice were developed separately, on different backgrounds; seven published Aire knockout mice show a variety of phenotypes depending on the strain used to generate the experimental model. The first Aire-deficient mice were generated on a "black 6" background almost 20 years ago. The model showed mild phenotype with relatively modest penetrance compared to models generated on BALBc or NOD backgrounds. The generation of all these experimental models is crucial for development and testing new therapeutics as well as reading the response to treatments.
Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with cutaneous hyper-reactivity to environmental triggers that are innocuous to normal, non-atopic individuals.1 Major contributors to this hyperactivity are the many changes in the cutaneous and systemic immune responses in individuals with AD.2 One example is the production of raised levels of total serum immunoglobulin IgE and specific IgE to common allergens.3 However, the link between AD and allergen-specific IgE remains hotly debated.4 A recent systematic review revealed that the association with raised IgE was much lower in children with mild to moderate AD than in children with severe disease.3It has been postulated that the non-allergic, intrinsic dermatitis could be a pure, transitional form of AD.5
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