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The relationship among androgens, insulin resistance and ghrelin polymorphisms in post-adolescent male patients with severe acne vulgaris.

ABSTRACT: Introduction:Ghrelin has anti-inflammatory and immunomodulatory activities. Data about the role of ghrelin and ghrelin polymorphisms in the development of acne vulgaris in post-adolescent male patients are limited. Aim:To evaluate the role of serum androgens, insulin resistance, ghrelin and ghrelin polymorphisms in severe acne vulgaris. Material and methods:Thirty-five post-adolescent male patients with a mean age of 28.0 ±5.4 years and 33 age-and BMI-matched controls were enrolled. Serum androgens, lipids, insulin sensitivity parameters and ghrelin levels were determined. The PCR method was used for GHRL polymorphisms (rs27647, rs696217 and rs34911341 genotypes). Results:Patients had similar anthropometric measures to controls, except a significantly higher WHR in patients (0.92 ±0.06 vs. 0.86 ±0.08, p < 0.05). Also, FPG, HOMA-IR values, lipid profile and serum androgen levels were similar. Interestingly, patients had significantly lower ghrelin levels than controls (4.5 ±5.8 vs. 101.2 ±86.5 pg/ml, p < 0.001). The frequencies of rs696217 and rs34911341 genotypes were similar whereas the distribution of rs27647 alleles was significantly different between the groups (p < 0.05). GA and GG genotypes of GHRL rs27647 polymorphism indicated an increased risk of developing acne vulgaris (OR = 11.156, 95% CI: 2.864-43.464, OR = 5.312, 95% CI: 1.269-22.244, respectively; p < 0.05). Patients with rs27647-AA polymorphism had significantly lower GAGS scores than other groups (AA genotype 6.7 ±14.1 vs. GA genotype 24.6 ±15.7 and GG genotype 19.4 ±17.9, p < 0.001). None of the polymorphisms had a significant effect on metabolic parameters, insulin sensitivity and serum ghrelin levels. Conclusions:Decreased ghrelin levels and GA and GG genotypes of GHRL gene rs27647 polymorphism may have a role in the pathogenesis of acne vulgaris.

SUBMITTER: Pektas SD

PROVIDER: S-EPMC7675091 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The relationship among androgens, insulin resistance and ghrelin polymorphisms in post-adolescent male patients with severe acne vulgaris.

Pektas Suzan Demir SD Cinar Nese N Duman Deniz Demircioglu DD Kara Ahmet A Batu Janserey J Karakas-Celik Sevim S Aksoy Duygu Yazgan DY

Postepy dermatologii i alergologii 20201001 5

<h4>Introduction</h4>Ghrelin has anti-inflammatory and immunomodulatory activities. Data about the role of ghrelin and ghrelin polymorphisms in the development of acne vulgaris in post-adolescent male patients are limited.<h4>Aim</h4>To evaluate the role of serum androgens, insulin resistance, ghrelin and ghrelin polymorphisms in severe acne vulgaris.<h4>Material and methods</h4>Thirty-five post-adolescent male patients with a mean age of 28.0 ±5.4 years and 33 age-and BMI-matched controls were ...[more]

PMID: 33240024

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Project description:ContextSyndromes of severe insulin resistance (SIR) include insulin receptoropathy, in which all signaling downstream of the insulin receptor is lost, and lipodystrophy, in which some signaling pathways are impaired and others preserved. Women with SIR commonly have ovarian hyperandrogenemia; adrenal-derived 11-oxygenated androgens, produced by CYP11B1, have not been studied.ObjectiveWe aimed to evaluate classic pathway androgens (androstenedione, testosterone) and 11-oxygenated androgens in women with SIR and hyperandrogenemia, and to elucidate the role of insulin receptor signaling for 11-oxygenated androgen production by comparing lipodystrophy and receptoropathy.MethodsSteroid hormones were quantified using LC-MS/MS in a cross-sectional study of 18 women with hyperandrogenemia and SIR (11 lipodystrophy, 7 receptoropathy) and 23 controls. To assess ovarian vs adrenal origin, steroids were compared in receptoropathy patients with (Ovary+) vs without (Ovary-) ovarian function.ResultsCompared with controls, classic androgens were elevated in both lipodystrophy and receptoropathy, and 11-oxygenated androgens were increased in lipodystrophy (2.9-fold higher 11β-hydroxyandrostenedione (11OHA4), 2.4-fold higher 11-ketoandrostenedione (11KA4), 3.6-fold higher 11-ketotestosterone (11KT); P < 0.01), but not receptoropathy. Product-to-precursor ratios for CYP11B1 conversion of androstenedione to 11OHA4 were similar in lipodystrophy and controls but decreased in receptoropathy (6.5-fold lower than control; P = 0.001). Classic androgens were elevated in Ovary + but not Ovary- patients.Conclusions11-Oxygenated androgens are elevated in lipodystrophy but not receptoropathy. In SIR, insulin receptor signaling is necessary for adrenal hyperandrogenemia but not ovarian hyperandrogenemia; excess classic androgens are derived from the ovaries. Insulin receptor signaling increases adrenal 19-carbon steroid production, which may have implications for more common disorders of mild IR.

Project description:Background and objectives: Acne vulgaris is a highly prevalent and multifactorial skin disorder that can adversely impact health-related quality of life. Factors that contribute to the pathogenesis of acne include pilosebaceous proliferation of proinflammatory Propionibacterium acnes (P. acnes) bacteria, presence of circulating androgens, excess sebum production, abnormal follicular keratinization, and multiple inflammatory cascades. Oral tetracyclines-especially doxycycline and minocycline-are frequently prescribed for the treatment of moderate-to-severe acne, given their anti-inflammatory properties and their effect on P. acnes reduction. Notwithstanding their established efficacy in the management of acne vulgaris, there is a desire to limit systemic exposure to antibiotics given growing concerns regarding bacterial resistance as well as the potential for serious side effects. This report describes outcomes of two randomized, vehicle-controlled trials (Phases IIa and IIb) of BPX-01, a topical minocycline gel, in the treatment of moderate-to-severe acne. Methods: In Study 1 (NCT02709096), at a single center, 33 subjects with highly fluorescing facial skin were randomized 2:1 to BPX-01 1% or vehicle control once-daily treatment for four weeks. Changes in P. acnes quantitative bacteriological cultures were assessed, as well as cutaneous tolerance to the study drug by both subjects and the investigator. In Study 2 (NCT02815332), subjects with moderate-to-severe inflammatory nonnodular acne (n=226) at 15 centers were randomized 1:1:1 to treatment with BPX-01 1%, BPX-01 2%, or vehicle control once-daily for 12 weeks. The primary endpoint was reduction in the number of inflammatory lesions; other endpoints included the number of noninflammatory lesions, Investigator's Global Assessment (IGA) of severity, and subjective ratings (investigator and subject) of acne. In both studies, cutaneous tolerability and safety were assessed, and plasma minocycline levels were tracked with a highly sensitive assay. Results: In Study 1, BPX-01 treatment reduced P. acnes colonization by 90.9 percent, which exceeded the reduction in the vehicle control group (65.53%; p=0.020). In Study 2, treatment with BPX-01 2% reduced the number of inflammatory lesions by 58.5 percent, exceeding the reduction in the vehicle control group (43.8%; p=0.0256). Trends toward an improvement preferential to BPX-01 2% were observed in the other endpoints. Across both studies, BPX-01 treatment was well-tolerated, with no photosensitivity, postinflammatory hyperpigmentation, or skin discoloration reported. A single subject (out of 259 study participants ) was identified to have detectable levels of plasma minocycline at low levels (42ng/mL) after 12 weeks of treatment but had no signs or symptoms associated with systemic administration of minocycline. Conclusion: BPX-01 appears to exhibit an effectiveness profile for reduction of inflammatory (nonnodular) acne lesions similar to that of oral minocycline formulations. However, because BPX-01 is topical and exhibits negligible systemic exposure, the likelihood of adverse events associated with oral minocycline use is much lower. These results demonstrate effectiveness of BPX-01 topical minocycline gel in reducing P. acnes colonization, suggesting that the BPX-01 2% formulation is a promising treatment for moderate-to-severe nonnodular, inflammatory acne vulgaris in both reduction of inflammatory lesions and also overall improvement in facial acne according to IGA.

Project description:ObjectiveAndrogens acting through the androgen receptor play a crucial role in the pathogenesis of acne. This study aimed to identify whether two key genes (CYP21A2 and CYP19A1) involved in the synthesis and metabolism of androgens were associated with Pillsbury III-IV severe acne vulgaris.MethodsWe carried out a standard questionnaire survey about acne and enlisted 600 Pillsbury III-IV severe acne vulgaris patients and 652 healthy controls of Han Chinese descent from Yunnan, China in the study. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot assay and analyzed for association with severe acne.ResultsThere was no significant difference in gender between the two groups (P = 0.085), and the age of the acne case group was significantly lower than that of the control group (P < 0.001). Our results revealed that only two SNPs, rs6474 (p.Arg102Lys) (P = 0.001) and rs6465 (P = 0.025) of the CYP21A2 gene were significantly associated with severe acne among the Han Chinese. When subjects were divided into males and females, significant associations were observed only in male patients with severe acne vulgaris for four variants: CYP21A2 rs6474 (p.Arg102Lys) (P = 0.002); CYP21A2 rs6465 (P = 0.012); CYP19A1 rs8023263 (P = 0.037); and CYP19A1 rs2470152 (P = 0.007). Haplotype analyses showed that the distribution of CYP21A2 haplotypes was significantly associated with male patients, while no association of CYP19A1 haplotypes was observed. The structure of the human CYP21A2 consists of two substrate binding sites and one substrate access channel.ConclusionThis study shed a light on a potentially important effect of CYP21A2 and CYP19A1 genes in severe acne vulgaris in the Han Chinese, especially for male patients. Future studies using independently verified datasets from a broader geographical spectrum will be valuable in identifying the causal and functional variants responsible for severe acne vulgaris within the CYP19A1 and CYP21A2 genes.

Dataset Information

The relationship among androgens, insulin resistance and ghrelin polymorphisms in post-adolescent male patients with severe acne vulgaris.

Publications

The relationship among androgens, insulin resistance and ghrelin polymorphisms in post-adolescent male patients with severe acne vulgaris.

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