Association between leptin gene rs7799039 polymorphism and lipid profile changes induced by isotretinoin treatment in acne patients

Khabour, Omar F.; Alzoubi, Karem H.; Firoz, Abdul S.; Al-Awad, Rafat Mm

doi:10.2147/tcrm.s165712

Cited by 9 publications

(6 citation statements)

References 47 publications

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“…Previous studies have shown that isotretinoin can alter human lipid metabolism by significantly reducing sebum production while raising blood lipids ( Khabour et al, 2018 ). Gencebay’s study showed a 36% decrease in sebum levels after 6 months of oral isotretinoin systemic therapy in patients with acne vulgaris ( Gencebay et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne

et al. 2022

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Background: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit. This study aimed to explore the pathogenesis of acne and the therapeutic mechanism of isotretinoin from the metabolic perspective in coal tar-induced acne in rabbits.Methods: Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was used to identify skin metabolites in groups C (blank control), M (model group) and T (isotretinoin group). Multivariate statistical analysis was used to process the metabolomics data.Results: 98 differential metabolites in group C and group M were identified. The highest proportion of differential metabolites were organic acids and derivatives, lipid metabolites, organic heterocyclic compounds, and nucleoside metabolites. The most significant metabolic pathways included protein digestion and absorption, central carbon metabolism in cancer, ABC transporters, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, and sphingolipid signaling pathway. Isotretinoin treatment normalized eight of these metabolites.Conclusions: Our study will help to further elucidate the pathogenesis of acne, the mechanism of isotretinoin at the metabolite level, and identify new therapeutic targets for treating acne.

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Section: Discussionmentioning

confidence: 99%

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne

et al. 2022

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“…On the contrary of our findings, a cross-sectional study had reported lower AST levels in LEP AA genotype in 200 AV patients treated with oral isotretinoin for 1 month. 35 This controversary may be due to difference in patients’ ethnicity or difference in isotretinoin treatment duration.…”

Section: Discussionmentioning

confidence: 99%

“…Our data is accordance with findings of a recent study which reported lower TC levels in LEP rs7799039 CC genotype in Jordanian AV patients who received 40 mg/day oral isotretinoin. 35 …”

Section: Discussionmentioning

confidence: 99%

Isotretinoin Induced Hyperlipidemia and Impact of Leptin Gene rs 7799039 Polymorphism in Safety of Acne Patients

Mohamed¹,

Hassnine²,

El-Sayed³

et al. 2021

PGPM

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Background Acne vulgaris (AV) is a chronic inflammatory disease that affects the pilosebaceous unit. Leptin (LEP) gene polymorphisms is associated with higher risk of multiple disorders. Insulin-like growth factor-1 (IGF-1) exerts comedogenic effect by stimulating the sebaceous glands. Isotretinoin is an effective oral therapy for AV with many side effects including hyperlipidemia and increased serum levels of liver enzymes. Purpose To evaluate the impact of LEP gene rs7799039 polymorphism in acne patients’ clinical response lipid profile and liver enzymes following 6 months oral isotretinoin therapy in Egyptian AV patients. Methods One hundred eligible AV patients received 0.5 mg/kg oral isotretinoin for 6 months. Patients’ demographics and clinical data were obtained. Body mass index (BMI), lipid profile, liver enzymes and IGF-1 were measured at baseline and after 6 months of therapy. Genotyping was done for LEP gene rs 7799039. Results Six month administration of oral isotretinoin in Egyptian AV patients is associated with significantly elevated aspartate transaminase (AST) in CC and AC genotypes (P<0.001). Significant alanine aminotransferase (ALT) elevation was observed in CC, AC and AA genotypes (P <0.001, 0.004, 0.002, respectively). Total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) were elevated significantly P<0.001) in the three genotypes. IGF-1 was decreased significantly in CC and AC genotypes (P<0.001). CC genotype is associated with highest response (P<0.001). Conclusion LEP rs7799039 gene had an impact on the clinical response, lipid profile and liver enzymes in AV patients treated with oral isotretinoin. LEP rs7799039 CC genotype is predicted to be the treatment candidate for 6 month oral isotretinoin.

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“…Alzoubi et al 7 revealed that polymorphisms of RARA gene were associated with some common adverse effects of oral isotretinoin. Khabour et al 8 found that lipid parameters and liver enzymes might be modulated by rs7799039 LEP polymorphism. Agamia et al 9 found the nucleocytoplasmic ratio of nonphosphorylated FoxO1 and FoxO3 significantly increased during isotretinoin treatment of acne patients.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome comparison of isotretinoin‐effective and isotretinoin‐ineffective severe acne vulgaris patients

Jiang

Zhang

Guo

et al. 2020

J of Cosmetic Dermatology

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Background Oral isotretinoin is the first‐line treatment of severe nodular acne. However, patients presenting ineffective or poor effective to oral isotretinoin are still a clinical problem, and its molecular genetic mechanisms remain unclear. Aims To compare the transcriptome profiles of isotretinoin‐effective and isotretinoin‐ineffective severe acne vulgaris patients and analyze the potential physiological roles to better understand the mechanisms of isotretinoin efficacy differences. Patients/Methods Peripheral blood of 43 patients with severe acne was collected before treatment. After 8‐week isotretinoin, patients presented effective and ineffective to isotretinoin treatment were selected and their pretreatment peripheral blood was analyzed. High‐throughput sequencing was used to detect gene expression profiles. Gene Ontology and KEGG were used to perform functional annotation and pathway enrichment analysis. Results Ten acne patients (3 male and 7 female, age 31 ± 9.2) presented effectiveness by oral isotretinoin and 10 acne patients (4 male and 6 female, age 28 ± 7.7) presented ineffectiveness were included. Comparison of gene profiles of isotretinoin‐effective and isotretinoin‐ineffective patients revealed 2779 differentially expressed genes: 2723 upregulated and 56 downregulated. Differentially expressed genes were enriched in RNA degradation pathway, autophagy pathway, protein ubiquitination pathway, protein processing in endoplasmic reticulum pathway, T‐cell receptor signaling pathway, spliceosome pathway, mRNA surveillance pathway, cell cycle pathway, long‐term potentiation pathway, and FoxO signaling pathway. Conclusion Transcriptome expression differences not only participated in the acne pathogenesis, but also influenced the isotretinoin therapeutic effects. These findings might provide some evidence for exploring individualized therapy for acne patients.

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Association between leptin gene rs7799039 polymorphism and lipid profile changes induced by isotretinoin treatment in acne patients

Cited by 9 publications

References 47 publications

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne

Nontargeted metabolomics to characterize the effects of isotretinoin on skin metabolism in rabbit with acne

Isotretinoin Induced Hyperlipidemia and Impact of Leptin Gene rs 7799039 Polymorphism in Safety of Acne Patients

Transcriptome comparison of isotretinoin‐effective and isotretinoin‐ineffective severe acne vulgaris patients

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