Abstract：
Recurrent vaginitis is a leading reason for visiting a gynaecologist, with bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) being the most common diagnoses. Reasons and mechanisms behind their recurrent nature are poorly understood. We conducted a genome-wide association study (GWAS) to find possible genetic risk factors for recurrent vaginitis using data from a large population-based biobank, the Estonian Biobank. The study included 6870 cases (at least two episodes of vaginitis) and 5945 controls (no vaginitis episodes). GWAS approach included single marker and gene-based analyses, followed by functional annotation of associated variants and candidate gene mapping.In single marker analysis, one statistically significant (P = 7.8 × 10-9) variant rs1036732378 was identified on chromosome 10. The gene-based association analysis identified one gene, KRT6A, that exceeded the recommended significance threshold (P = 2.6 × 10-6). This is a member of the keratin protein family and is expressed during differentiation in epithelial tissues.Functional mapping and annotation of genetic associations by using adjusted significance level identified 22 potential risk loci that may be associated with recurrent vaginitis phenotype. Comparison of our results with previous studies provided nominal support for LBP (associated with immune response to vaginal bacteria) and PRKCH genes (possible role in keratinocyte differentiation and susceptibility to candidiasis).In conclusion, this study is the first highlighting a potential role of the vaginal epithelium in recurrent vaginitis.
摘要：
复发性阴道炎是拜访妇科医生的主要原因，细菌性阴道病（BV）和外阴阴道念珠菌病（VVC）是最常见的诊断。其经常性背后的原因和机制知之甚少。我们进行了一项全基因组关联研究（GWAS），以发现复发性阴道炎可能的遗传风险因素，使用来自大型人群的生物样本库的数据，爱沙尼亚生物库。该研究包括6870例（至少两次阴道炎发作）和5945例对照（无阴道炎发作）。GWAS方法包括单标记和基于基因的分析，然后是相关变体的功能注释和候选基因定位。在单标记分析中，在10号染色体上鉴定出一个具有统计学意义（P=7.8×10-9）的rs1036732378变体。基于基因的关联分析确定了一个基因，KRT6A,超过推荐的显著性阈值(P=2.6×10-6)。这是角蛋白家族的成员并且在上皮组织的分化过程中表达。通过使用调整的显著性水平鉴定的22个可能与复发性阴道炎表型相关的潜在风险基因座的遗传关联的功能作图和注释。我们的结果与先前研究的比较为LBP（与对阴道细菌的免疫反应相关）和PRKCH基因（在角质形成细胞分化和念珠菌病易感性中的可能作用）提供了名义上的支持。总之,这项研究首次强调了阴道上皮在复发性阴道炎中的潜在作用。
