The Associations of Androgen-Related Genes CYP21A2 and CYP19A1 with Severe Acne Vulgaris in Patients from Southwest China

Ting Yang; Wen-Juan Wu; Li-Ming Tian; Deng-Feng Zhang; Xiao-Yan Yang; Jue Qi; Ying Tu; Li He

doi:10.2147/CCID.S293171

The Associations of Androgen-Related Genes CYP21A2 and CYP19A1 with Severe Acne Vulgaris in Patients from Southwest China

Clin Cosmet Investig Dermatol. 2021 Mar 29:14:313-331. doi: 10.2147/CCID.S293171. eCollection 2021.

Authors

Ting Yang^{1

2}, Wen-Juan Wu¹, Li-Ming Tian³, Deng-Feng Zhang⁴, Xiao-Yan Yang¹, Jue Qi¹, Ying Tu¹, Li He¹

Affiliations

¹ Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650023, People's Republic of China.
² Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, 435000, People's Republic of China.
³ Department of Dermatology, First Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People's Republic of China.
⁴ Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, People's Republic of China.

Abstract

Objective: Androgens acting through the androgen receptor play a crucial role in the pathogenesis of acne. This study aimed to identify whether two key genes (CYP21A2 and CYP19A1) involved in the synthesis and metabolism of androgens were associated with Pillsbury III-IV severe acne vulgaris.

Methods: We carried out a standard questionnaire survey about acne and enlisted 600 Pillsbury III-IV severe acne vulgaris patients and 652 healthy controls of Han Chinese descent from Yunnan, China in the study. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot assay and analyzed for association with severe acne.

Results: There was no significant difference in gender between the two groups (P = 0.085), and the age of the acne case group was significantly lower than that of the control group (P < 0.001). Our results revealed that only two SNPs, rs6474 (p.Arg102Lys) (P = 0.001) and rs6465 (P = 0.025) of the CYP21A2 gene were significantly associated with severe acne among the Han Chinese. When subjects were divided into males and females, significant associations were observed only in male patients with severe acne vulgaris for four variants: CYP21A2 rs6474 (p.Arg102Lys) (P = 0.002); CYP21A2 rs6465 (P = 0.012); CYP19A1 rs8023263 (P = 0.037); and CYP19A1 rs2470152 (P = 0.007). Haplotype analyses showed that the distribution of CYP21A2 haplotypes was significantly associated with male patients, while no association of CYP19A1 haplotypes was observed. The structure of the human CYP21A2 consists of two substrate binding sites and one substrate access channel.

Conclusion: This study shed a light on a potentially important effect of CYP21A2 and CYP19A1 genes in severe acne vulgaris in the Han Chinese, especially for male patients. Future studies using independently verified datasets from a broader geographical spectrum will be valuable in identifying the causal and functional variants responsible for severe acne vulgaris within the CYP19A1 and CYP21A2 genes.

Keywords: androgen receptor; genetic risk; metabolism; severe acne; synthesis.

Grants and funding

This study was supported by the National Natural Science Foundation of China (81960563, 81760559), Yunnan Science and Technology Leading Talents Project (2017HA010), Huangshi Science and Technology Bureau and Health Bureau joint fund (2016).