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Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles.

ABSTRACT: Skin disease alters cutaneous lipid mediator metabolism, and if skin secretions contain evidence of these changes, they may constitute useful clinical matrices with low associated subject burden. The influences of skin diseases on sebum lipid mediators are understudied. Here, sebum oxylipins, endocannabinoids, sphingolipids, and fatty acids were quantified from the non-lesional bilateral cheeks of subjects with and without quiescent atopic dermatitis (AD) using LC-MS/MS and GC-MS. AD decreased C36 [NS] and [NdS] ceramide concentrations. Compared to males, females demonstrated increased concentrations of oxylipin alcohols and ketones, and saturated and monounsaturated non-esterified fatty acids, as well as decreased concentrations of C42 [NS] and [NdS] ceramides. Additionally, contemporaneously collected sweat lipid mediator profiles were distinct, with sebum showing higher concentrations of most targets, but fewer highly polar lipids. Therefore, AD and gender appear to alter sebum lipid metabolism even in non-lesional skin of quiescent subjects.

SUBMITTER: Agrawal K

PROVIDER: S-EPMC6800162 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles.

Agrawal Karan K Hassoun Lauren A LA Foolad Negar N Borkowski Kamil K Pedersen Theresa L TL Sivamani Raja K RK Newman John W JW

Prostaglandins, leukotrienes, and essential fatty acids 20180517

Skin disease alters cutaneous lipid mediator metabolism, and if skin secretions contain evidence of these changes, they may constitute useful clinical matrices with low associated subject burden. The influences of skin diseases on sebum lipid mediators are understudied. Here, sebum oxylipins, endocannabinoids, sphingolipids, and fatty acids were quantified from the non-lesional bilateral cheeks of subjects with and without quiescent atopic dermatitis (AD) using LC-MS/MS and GC-MS. AD decreased C ...[more]

PMID: 29886894

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Project description:BackgroundSome evidence suggests abnormalities in fatty acids in patients with atopic dermatitis (AD), and benefits of supplementation with these fatty acids have been reported. However, there is still substantial controversy on the correlation between fatty acids and AD. Therefore, the aim of this study was to determine whether fatty acid levels are causally related to AD using a Mendelian randomization approach.MethodsWe evaluated the data about the fatty acids levels and AD with various methods from Genome-Wide Association Study (GWAS). GWAS results were available both from European ancestry. Mendelian randomization methods were used to analysis the casual inference of fatty acids on AD. MR Egger and MR-PRESSO were used to determine pleiotropy and heterogeneity. Further analysis was conducted using instruments associated with the FADS genes to address mechanisms involved. We also used Multivariate MR (MVMR) to show the independent casual inference of omega-3 (n-3) fatty acids on AD.ResultsMendelian randomization (MR) analysis suggests that n-3 fatty acid levels are associated with a lower risk of AD (n-3 ORIVW: 0.92, 95% confidence interval [CI]: 0.87-0.98; p = 0.01). Moreover, docosahexaenoic acids (DHA) levels, which is a kind of long-chain, highly unsaturated omega-3 (n-3) fatty acid, and its higher level was associated with a lower risk of AD (DHA ORIVW: 0.91, 95% CI: 0.84-0.98; p = 0.02). We ran multivariable MR analysis while controlling for variables within the other types of fatty acids. The effect estimates agreed with the preliminary MR analysis indicating the effect of n-3 fatty acids levels on AD was robust. MR-egger suggest no significant pleiotropy and heterogeneity on genetic instrumental variants. Outliers-corrected MR analyses after controlling horizontal pleiotropy were still robust. The single-SNP analyses revealed that n-3 fatty acids are likely linked to a decreased risk of AD through FADS cluster, highlighting the significance of the FADS gene in the fatty acids synthesis pathway in the development of AD.ConclusionOur studies suggest that n-3 fatty acids may reduce the risk of AD. Risk prediction tools based on n-3 fatty acid levels may be valuable methods for improving AD screening and primary prevention. To reduce the risk of AD, individuals could enhance n-3 fatty acids intake through supplement or diet.

Project description:BackgroundAtopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD.ObjectiveWe sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD.MethodsA total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined.ResultsAmong VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels.ConclusionsThe VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.

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Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles.

Publications

Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles.

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