Moreau Karen, Clemenceau Alisson, Le Moing Vincent, Messika-Zeitoun David, Andersen Paal S, Bruun Niels E, Skov Robert L, Couzon Florence, Bouchiat Coralie, Erpelding Marie L, van Belkum Alex, Bossé Yohan, Duval Xavier, Vandenesch Francois
International Center for Infectiology Research, CNRS UMR5308, INSERM U1111, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon, France.
Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval, Quebec City, QC, Canada.
Front Microbiol. 2018 Apr 4;9:640. doi: 10.3389/fmicb.2018.00640. eCollection 2018.
infective endocarditis (SaIE) is a severe complication of bacteremia (SAB) occurring in up to 22% of patients. Bacterial genetic factors and host conditions for SaIE have been intensely studied before; however, to date no study has focused on predisposing host genetic factors to SaIE. The present study aimed to identify genetic polymorphisms associated with SaIE by a Genome-Wide Association Study (GWAS) of 67 patients with definite native valve SaIE (cases) and 72 matched native valve patients with SAB but without IE (controls). All patients were enrolled in the VIRSTA cohort (Le Moing et al., 2015) study. Four single nucleotide polymorphisms (SNPs) located on chromosome 3 were associated with SaIE ( < 1 × 10) without reaching conventional genome-wide significance. For all, the frequency of the minor allele was lower in cases than in controls, suggesting a protective effect of the minor allele against SaIE. The same association was observed using an independent Danish verification cohort of SAB with ( = 57) and without ( = 123) IE. analysis of aortic valve tissues revealed that SaIE associated SNPs mentioned above were associated with significantly higher mRNA expression levels of SLC7A14, a predicted cationic amino acid transporter protein. Taken together, our results suggest an IE-protective effect of SNPs on chromosome 3 during the course of SAB. The effects of protective minor alleles may be mediated by increasing expression levels of SLC7A14 in valve tissues. We conclude that occurrence of SaIE may be the combination of a well-adapted bacterial genotype to a susceptible host.
感染性心内膜炎（SaIE）是菌血症（SAB）的一种严重并发症，在高达22%的患者中发生。此前已对SaIE的细菌遗传因素和宿主状况进行了深入研究；然而，迄今为止，尚无研究关注宿主遗传因素对SaIE的易感性。本研究旨在通过对67例确诊为天然瓣膜SaIE的患者（病例组）和72例匹配的患有SAB但无IE的天然瓣膜患者（对照组）进行全基因组关联研究（GWAS），以确定与SaIE相关的基因多态性。所有患者均纳入VIRSTA队列（Le Moing等人，2015年）研究。位于3号染色体上的四个单核苷酸多态性（SNP）与SaIE相关（<1×10），但未达到传统的全基因组显著性水平。总体而言，病例组中次要等位基因的频率低于对照组，表明次要等位基因对SaIE有保护作用。在一个独立的丹麦SAB验证队列中，有IE（=57）和无IE（=123）的患者也观察到了相同的关联。对主动脉瓣组织的分析显示，上述与SaIE相关的SNP与预测的阳离子氨基酸转运蛋白SLC7A14的mRNA表达水平显著升高有关。综上所述，我们的结果表明，在SAB过程中，3号染色体上的SNP对IE有保护作用。保护性次要等位基因的作用可能是通过增加瓣膜组织中SLC7A14的表达水平来介导的。我们得出结论，SaIE的发生可能是适应性良好的细菌基因型与易感宿主共同作用的结果。
