Abstract
BackgroundMultiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors.MethodsWe performed a systematic review on the genes and their variants that have been investigated for association with acne presentation and severity. A random-effect meta-analysis using the allele model (minor allele vs. major allele) was also conducted to provide an overall estimation of risk effects of frequently reported gene variants. This included a subset data of 982 acne cases and 846 controls extracted from our existing GWAS database on various allergic and skin diseases among Singapore Chinese.ResultsSystematic review of 51 articles covering Asians and Caucasians found 60 genes/loci and their 100 variants implicated in acne; majority of them were in the intron, coding region/missense, and promoter regions. The commonly studied candidate genes/gene families include tumor necrosis factor (TNF), and the interleukin (IL) and cytochrome P450 (CYP) gene families. Our meta-analysis showed that most of the analyzed gene variants exhibited insignificant pooled odds ratio (pOR) and significant heterogeneity between studies. Nevertheless, we found that TNF rs1800629 A allele carriers and CYP17A1 rs743572 T allele carriers had significantly reduced mild acne risk [pOR: 0.60; 95% Confidence Interval (CI): 0.33–0.86] and severe acne risk (pOR: 0.59; 95% CI: 0.40–0.79), respectively, across populations. Overall, FST (follistatin) rs629725 A allele poses a significantly modest increased risk for acne presentation (pOR: 1.19, 95% CI: 1.14, 1.23), but neither TIMP2 (TIMP metallopeptidase inhibitor 2) rs8179090 nor CYP1A1 rs4646903 (pOR: 0.96, 95% CI: 0.80–1.12; pOR: 0.95, 95% CI: 0.83, 1.08), respectively. We discovered 15 novel SNPs in the 3′ UTR region of the Toll-like Receptor 4 gene (TLR4) associated with acne presentation.ConclusionsThis systematic review and meta-analysis suggest that genes influencing inflammatory responses, specifically TNF, and genes influencing the function and activity of sebaceous glands, specifically CYP17A1 and FST, have potential risk variants for acne presentation and severity across populations. Understanding the genetic susceptibility factors and biological pathways involved in the pathogenesis of acne will help us to gain insights into developing effective acne treatments.
Highlights
Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors
Most of the genes identified in the reviewed studies and from DAVID analysis can be categorized into two major biological function groups, namely ‘immune and inflammatory responses’ and ‘sebaceous gland function and activity’ (Table 1)
The reviewed papers reported on genes and their variants associated with the risk of acne presentation and severity
Summary
Multiple factors have been attributed to acne vulgaris predisposition and individual variations in the severity of skin symptoms, and genetics stood out as one of the major factors. Recent candidate gene studies and genome-wide association studies (GWAS) further revealed that the genes and loci associated with acne presentation and severity influence the function and activity of sebaceous glands or immune and inflammatory responses (reviewed in 9,10). Two such gene susceptibility loci were found in Han Chinese [9], while up to 15 were found in Caucasians [10,11,12]
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