Allergy and Molecular Immunology Laboratory, Lee Hiok Kwee Functional Genomics Laboratories, Department of Biological Sciences, Faculty of Science, National University of Singapore, Block S2, Level 5, 14 Science Drive 4, Lower Kent Ridge Road, Singapore, 117543, Singapore.
BMC Med Genomics. 2021 Apr 13;14(1):103. doi: 10.1186/s12920-021-00953-8.
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.
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.
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.
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.
多种因素可导致寻常痤疮易感性和皮肤症状严重程度的个体差异，而遗传是主要因素之一。
我们对与痤疮表现和严重程度相关的基因及其变异进行了系统评价。还使用等位基因模型（次要等位基因与主要等位基因）进行了随机效应荟萃分析，以提供经常报道的基因变异风险效应的总体估计。这包括从我们现有的新加坡华人各种过敏和皮肤病的 GWAS 数据库中提取的 982 例痤疮病例和 846 例对照的亚组数据。
对涵盖亚洲人和高加索人的 51 篇文章进行的系统评价发现了 60 个与痤疮相关的基因/基因座及其 100 个变异体；其中大多数位于内含子、编码区/错义突变和启动子区域。常用的候选基因/基因家族包括肿瘤坏死因子（TNF）和白细胞介素（IL）和细胞色素 P450（CYP）基因家族。我们的荟萃分析表明，大多数分析的基因变异体显示出无统计学意义的汇总优势比（pOR）和研究之间存在显著异质性。然而，我们发现 TNF rs1800629 A 等位基因携带者和 CYP17A1 rs743572 T 等位基因携带者的轻度痤疮风险显著降低[OR：0.60；95%置信区间（CI）：0.33-0.86]和严重痤疮风险（OR：0.59；95% CI：0.40-0.79），在不同人群中。总体而言，FST（卵泡抑素）rs629725 A 等位基因显著增加痤疮发生的风险（OR：1.19，95% CI：1.14，1.23），但 TIMP2（TIMP 金属蛋白酶抑制剂 2）rs8179090 和 CYP1A1 rs4646903 均无显著影响（OR：0.96，95% CI：0.80-1.12；OR：0.95，95% CI：0.83，1.08）。我们在 Toll 样受体 4 基因（TLR4）的 3'UTR 区域发现了 15 个与痤疮表现相关的新 SNP。
本系统评价和荟萃分析表明，影响炎症反应的基因，特别是 TNF，以及影响皮脂腺功能和活性的基因，特别是 CYP17A1 和 FST，在不同人群中具有潜在的痤疮发生和严重程度的风险变异体。了解寻常痤疮发病机制中的遗传易感性因素和生物学途径将有助于我们深入了解有效的痤疮治疗方法。
