The Relationship Between CYP21A2Polymorphism And Acne In The Han Ethnic Group

Background:Acne with different symptoms is one of the most common chronic inflammation diseases of pilosebaceous gland. Current research indicates that the pathogenesis of acne involves4main processes:follicular hyperproliferation, excess sebum production, inflammation, and proliferation of Propionibacterium acnes. Seborrhea is recognized as one pathogenic factor for acne. Sebum production is regulated by androgens, and androgen excess may provoke or aggravate acne in susceptible individuals. Increased serum androgen levels correlated with the presence of severe nodular acne in men and women.CYP21A2gene is located on chromosome6p21.3, encoding adrenal21-hydroxylase (21-OH) which catalyses the conversion of17-hydroxyprogesterone (17-OHP) to11-deoxycorticosterone. Its inactivation or dysfunction results in reduced glucocorticoid and increased androgen production. But the relationship between CYP21A2and acne isn’t established.Objective:The aim of our study was to investigate the relationship between the single nucleotide polymorphism of androgen related gene CYP21A2and acne susceptibility.Methods:5tag and function SNPs (rs6464, rs6465, rs6467, rs6472, rs6474) with an r2threshold of0.8were selected from the International HapMap Database Release and NCBI. All of them had a minor allele frequency (MAF) of≥0.1.300acne patients were included in the study. DNA was extracted from peripheral blood of individual patients. Patients with Polycystic Ovary Syndrome (PCOS), Seborrheic Alopecia and other immune system diseases were excluded from the study. A polymerase chain reaction (PCR) sequencing technique was used to amplify CYP21A2gene. A χ2test was used for data analysis and genotype was compared in different severity groups. Fisher’s exact test was necessary when more than20%cells’ values were smaller than five. Results:1. Rs6465and rs6474were excluded because they didn’t comply with Hardy-Weinberg equilibrium (HWE) at the P=0.01and P=0.00levels respectively.2. Rs6467was also excluded because the allele frequency was0.00(MAF=0.00) in our test.3. For locus rs6464in CYP21A2gene, the frequency distribution of the C/C homozygotes was significantly different between mild (Ⅰ°) group and moderate+sever (Ⅱ°+Ⅲ°+Ⅳ°) group in the recessive genetic model (P=0.044, OR=0.308). But allelic frequencies were not significantly different within groups (χ2=2.914, P=0.088).4. For locus rs6472in CYP21A2gene, no statistically significant difference was observed in genotype and allele distribution between the two groups.5. The analysis suggested that the LD between rs6464and rs6472was strong, D’was0.9185and r2was0.416(x2=134.8, P=0). In dominant model, haplotype of C-G was associated with moderate and severe acne (P=0.0447, OR=0.5652).Conclusions:1. This study provides the database of rs6464and re6472of CYP21A2alleles, genotypes and haplotypes in Chinese Hans people with acne.2. We first studied the SNPs of CYP21A2association with acne in Chinese Hans. Our findings suggest that SNP rs6464is associated with susceptibility to acne in recessive model. It may be markers for general susceptibility to acne. The haplotype of C-G was associated with moderate and severe acne in dominant model. It was found as high-risk ones in developing acne in this study.3. This study showed the CYP21A2correlation with different severity of acne. The different of acne may have different genetic background.4. The results of the study provide information for researching association of CYP21A2with acne and searching for susceptibility gene further.