Genetic predictors for bacterial vaginosis in women living with and at risk for HIV infection

IF 2.5 3区 医学 Q3 IMMUNOLOGY
Kerry Murphy, Quihu Shi, Donald R. Hoover, Adaora A. Adimora, Maria L. Alcaide, Susan Brockmann, Elizabeth Daubert, Priya Duggal, Daniel Merenstein, Jodie A. Dionne, Anandi N. Sheth, Marla J. Keller, Betsy C. Herold, Kathryn Anastos, Bradley Aouizerat
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引用次数: 0

Abstract

Problem

Bacterial vaginosis (BV) disproportionally impacts Black and Hispanic women, placing them at risk for HIV, sexually transmitted infections and preterm birth. It is unknown whether there are differences by genetic ancestry in BV risk or whether polymorphisms associated with BV risk differ by ancestry.

Methods

Women's Interagency HIV Study (WIHS) participants with longitudinal Nugent scores were dichotomized as having (n = 319, Nugent 7–10) or not having BV (n = 367, Nugent 0–3). Genetic ancestry was defined by clustering of principal components from ancestry informative markers and further stratified by BV status. 627 single nucleotide polymorphisms (SNPs) across 41 genes important in mucosal defense were identified in the WIHS GWAS. A logistic regression analysis was adjusted for nongenetic predictors of BV and self-reported race/ethnicity to assess associations between genetic ancestry and genotype.

Results

Self-reported race and genetic ancestry were associated with BV risk after adjustment for behavioral factors. Polymorphisms in mucosal defense genes including syndecans, cytokines and toll-like receptors (TLRs) were associated with BV in all ancestral groups.

Conclusions

The common association of syndecan, cytokine and TLR genes and the importance of immune function and inflammatory pathways in BV, suggests these should be targeted for further research on BV pathogenesis and therapeutics.

感染艾滋病毒和有感染风险的妇女细菌性阴道病的遗传预测因素。
问题:细菌性阴道病(BV)对黑人和西班牙裔女性的影响尤为严重,使她们面临感染 HIV、性传播感染和早产的风险。目前尚不清楚细菌性阴道病的风险是否因遗传血统而异,也不清楚与细菌性阴道病风险相关的多态性是否因血统而异:妇女机构间艾滋病研究(WIHS)参与者的纵向纽金特得分被二分为有 BV(n = 319,纽金特 7-10)或无 BV(n = 367,纽金特 0-3)。遗传祖先通过祖先信息标记的主成分聚类来定义,并根据 BV 状态进一步分层。在 WIHS GWAS 中发现了 627 个单核苷酸多态性 (SNP),涉及 41 个对粘膜防御很重要的基因。逻辑回归分析对 BV 的非遗传预测因素和自我报告的种族/族裔进行了调整,以评估遗传血统与基因型之间的关联:结果:在对行为因素进行调整后,自我报告的种族和遗传血统与 BV 风险有关。在所有祖先群体中,粘膜防御基因(包括辛迪加、细胞因子和收费样受体(TLRs))的多态性与 BV 相关:综合征蛋白、细胞因子和 TLR 基因的共同关联性以及免疫功能和炎症通路在 BV 中的重要性,表明这些基因应成为 BV 发病机制和治疗方法进一步研究的目标。
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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
314
审稿时长
2 months
期刊介绍: The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.
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