Gene variants associated with acne vulgaris presentation and severity: a systematic review and meta-analysis

Abstract

Background 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. Methods We 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. Results Systematic 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. Conclusions This 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.

Magnitude and temporal trend of acne vulgaris burden in 204 countries and territories from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019*

“…For example, a population‐based study in the USA showed that the disease burden for patient with light‐coloured skin is heavier 30 . Moreover, a recent systematic review on gene variants implicated in acne vulgaris reported that genes for immune and inflammatory response, especially tumour necrosis factor, and genes for sebaceous gland function and activity, CYP17A1 and FST in particular, were associated with acne presentation and severity 31 . Similar to almost all studies of global epidemiological burden, the heterogeneity in healthcare services, diagnostic methods, diagnostic evaluation standards, and dermatologists’ insights in these countries and even subnational regions could influence both the geographical differences and the temporal trends.…”

The Role of Skin Immune System in Acne

“…Acne vulgaris is a disease for which its occurrence and severity depend on various factors. These include, e.g., demographic, diet and lifestyle, and hormonal and genetic factors [ 47 ]. Current scientific reports on genes related to clinical symptoms and acne severity are scarce.…”

“…Recent genome-wide studies have shown that genes associated with acne influence sebaceous gland functions or the development of an inflammatory immune response [ 48 , 49 ]. The TNF gene variants located on chromosome 6p21.33 are the most frequently studied genes in terms of the severity of acne lesions caused by pro-inflammatory immune responses [ 47 ]. The studies present that the crucial variants are variability in positions -308, -238, -863, -857, and -1031 TNF SNP in acne [ 50 , 51 ].…”

“…The studies present that the crucial variants are variability in positions -308, -238, -863, -857, and -1031 TNF SNP in acne [ 50 , 51 ]. The polymorphism of genes for interleukins (IL) such as IL1A , IL1B , IL4 , IL6 , IL8 , IL10 , IL17A , IL17F , and related antagonists and receptors IL1RN , IL4R , IL17RB , and IL23R family genes are also responsible for the develop inflammation during acne vulgaris [ 47 ].…”

“…The groups of genes related to acne and a serious risk of acne can affect the function and activity of sebaceous glands. The families of the cytochrome P450 (CYP) gene and the 3-β HSD family (HSD3B) are two frequently examined families in analysis with respect to acne vulgaris [ 47 , 52 , 53 ].…”