Carrier status for steroid 21‐hydroxylase deficiency is only one factor in the variable phenotype of acne

Ostlere, L.S.; Rumsby, Gillian; Holownia, Peter; Jacobs, Howard S.; Rustin, M.H.A.; Honour, John W.

doi:10.1046/j.1365-2265.1998.3811205.x

Cited by 62 publications

(40 citation statements)

References 34 publications

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“…This is in agreement with observations that heterozigosity for CYP21 mutations may result in mild abnormalities of androgen biosynthesis reflected by higher mean free testosterone (13,30) or by higher mean DHEAS concentrations (10). Our results suggest that, in contrast with findings in patients with NC-CAH, among hyperandrogenic women, basal or ACTHstimulated 17-OHP concentrations are not a good indicator of the carrier status for inherited defects of CYP21, as observed also by other investigators (13,31,32) who defined the carrier status by molecular analysis of CYP21 gene, the most accurate method to define carriers for inherited defects of CYP21 (10). Older studies reported that the majority of heterozygotes for 21-hydroxylase deficiency can be detected by measuring the 17-OHP concentration 60 min after ACTH stimulation; however, the diagnosis of 21-hydroxylase deficiency was based on HLA genotyping (33 It remains unclear what was the cause of borderline elevations in ACTH-stimulated 17-OHP concentrations in nine of 12 hyperandrogenic patients (75%), in whom even extensive sequencing of the CYP21 gene and its proximal promoter region revealed no mutations.…”

Section: Discussioncontrasting

confidence: 57%

Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status

Dolžan¹,

Preželj²,

Vidan-Jeras³

et al. 1999

European Journal of Endocrinology

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Objective: To study the incidence of 21-hydroxylase deficiency in Slovenian hyperandrogenic women, at the gene level. Previous endocrine studies indicated large differences in the incidence of 21-hydroxylase deficiency in hyperandrogenic women. The predictive values of the 17-hydroxyprogesterone (17-OHP) response to ACTH stimulation and of HLA typing in screening for carrier status were re-evaluated. Design: Molecular analysis of CYP21 gene, ACTH stimulation and human leucocyte antigen (HLA) typing were performed in 83 consecutive Slovenian hyperandrogenic women. Measurements: Cortisol and 17-OHP concentrations were measured at baseline and 60 min after ACTH stimulation. Basal adrenal androgen concentrations were also measured. Results: None of 83 hyperandrogenic patients was affected with non-classical 21-hydroxylase deficiency, but 12 of 81 patients (14.8%) had high concentrations of 17-OHP after stimulation, indicative of carrier status. The increase in 17-OHP concentrations could be explained by a carrier status for CYP21 gene mutations in only three of 12 patients (25%), whereas seven of 69 patients (10.1%) with normal concentrations of 17-OHP after stimulation were found to be carriers of CYP21 gene mutations, indicating low positive predictive values of ACTH stimulation as a screening test for carriers of 21-hydroxylase deficiency. In total, 11 carriers were identified among 83 patients: seven CYP21 gene deletions/conversions, two Gln

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Section: Discussioncontrasting

confidence: 57%

Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status

Dolžan¹,

Preželj²,

Vidan-Jeras³

et al. 1999

European Journal of Endocrinology

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“…The first systematic molecular genetic analyses of a genetic predisposition to acne were performed only in the 1990s [33][34][35], and since that time only a small number of publications have emerged. Most of the genes studied so far are either key players of innate immune events during lesion formation or have a function in steroid hormone metabolism (Table 1); recently additional polymorphisms and mutations that can be linked to cellular metabolic processes have been published.…”

Section: Molecular Genetic Studiesmentioning

confidence: 99%

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

Szabó

Kemény

2011

Human Immunology

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A B S T R A C TAcne is one of the most common dermatologic diseases in the developed regions of the world, affecting a large percentage of the population. Despite the great improvement in the number and quality of studies of the molecular etiology of this disease in the past 3 decades, the detailed molecular pathogenesis and the cause of the large individual variations in severity of skin symptoms remain unknown. The roles of genetic inheritance and special genetic susceptibility and protective factors have been suggested for over 100 years, but their identification and determination started only in the 1990s. To date, only a small number of genetic polymorphisms affecting the expression and/or function of a handful of genes have been investigated. This review surveys the major findings of the classic and molecular genetic studies that have been conducted in this field, draws conclusions, and indicates how the available data help our current understanding of the pathogenesis of this common skin disease. ᭧

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“…Several candidate genes have thus far been implicated, which include tumour necrosis factor (TNF) 10,11 , tumour necrosis factor receptor 2 (TNFR2) 12 , tolllike receptor 2 (TLR2) 12 , interleukin 1-alpha (IL-1a) 13 , cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) 14 , cytochrome P450 family 17 subfamily A polypeptide 1 (CYP17A1) 15 , cytochrome P450 family 21 subfamily A polypeptide 2 (CYP21A2) 16 and androgen receptor (AR) 17 . These genes affect two major cellular processes: regulation of steroid hormone metabolism and the innate immune functions of epidermal keratinocytes.…”

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confidence: 99%

Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne

Yang

et al. 2014

Nat Commun

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Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P combined ¼ 4.41 Â 10 À 9 and rs1060573, P combined ¼ 1.28 Â 10 À 8 ) and 1q24.2 (SELL, rs7531806, P combined ¼ 1.20 Â 10 À 8 ) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.

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Carrier status for steroid 21‐hydroxylase deficiency is only one factor in the variable phenotype of acne

Cited by 62 publications

References 34 publications

Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status

Adrenal 21-hydroxylase gene mutations in Slovenian hyperandrogenic women: evaluation of corticotrophin stimulation and HLA polymorphisms in screening for carrier status

Studying the genetic predisposing factors in the pathogenesis of acne vulgaris

Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne

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