Abstract
Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL-6, and TNFα genes. The polymorphisms in promoter and intron region of the resistin gene affect its expression levels. Therefore, we explored the association of resistin polymorphisms (RETN +299G > A and −420C > G) with pathogenesis of acne vulgaris. We used PCR–RFLP method to genotype at the two single nucleotide polymorphisms at RETN promoter in 530 acne patients vs. 550 age- and sex-matched control subjects. We also measured serum lipid levels in acne patients and associated these with RETN genotypes. We found that the RETN gene polymorphisms are strongly associated with acne vulgaris and the severity of acne symptoms. In females the variant allele frequencies of both SNPs are statistically higher in patients than in controls; in males frequency distribution does not reach significance. The haplotype containing both variant alleles is significantly more common in patients than in controls. We find no association of RETN SNPs with the acne types. Importantly, we found that the levels of HDL-C were significantly decreased in variant genotype of RETN. Our results show that the RETN polymorphisms expected to boost resistin expression increase the risk of developing acne. We suggest that resistin may provide an attractive target for treatment.
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Acknowledgements
We acknowledge Dr. M. Jawad Hassan (Assistant Professor Healthcare Biotechnology, Atta ur Rahman School of Applied Biosciences NUST, Sector H-12, Islamabad, Pakistan) and Dr. Nazish Mehmood Aisha (Department of Dermatology WAPDA Hospital, Ferozpur Road Lahore Pakistan) for their help in acne patients sample collection from WAPDA Hospital, Lahore. This work has been supported by IRSIP, Higher Education Commission, Islamabad, Pakistan. Dr. Blumenberg’s research is supported by R.O.Perelman Department of Dermatology, NYU Medical School, New York, USA.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Written informed consent was obtained from all participants. The research was reviewed and approved by the Institutional Review Board, Quaid-i-Azam University.
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Younis, S., Blumenberg, M. & Javed, Q. Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation. Arch Dermatol Res 308, 229–237 (2016). https://doi.org/10.1007/s00403-016-1626-y
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DOI: https://doi.org/10.1007/s00403-016-1626-y