Han Wanda G H, Hodemaekers Hennie M, Nagarajah Bhawani, Poelen Martien M C, Helm Kina, Janssen Riny, van Els Cécile A C M
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, the Netherlands.
PLoS One. 2016 Feb 19;11(2):e0149576. doi: 10.1371/journal.pone.0149576. eCollection 2016.
Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1-10% in the general population, notifications of symptomatic pertussis only comprise 0.01-0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFα, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D3 (VD3) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection.
百日咳由革兰氏阴性的百日咳博德特氏菌感染引起，是一种严重的呼吸道疾病，可持续数月。虽然据估计普通人群中百日咳博德特氏菌的感染率在1%至10%之间，但有症状百日咳的报告仅占0.01%至0.1%，这表明大多数人在未出现（严重）临床症状的情况下清除了百日咳博德特氏菌感染。在本研究中，我们调查了遗传风险因素是否参与百日咳博德特氏菌感染后有症状百日咳的发生。在一组独特的荷兰有症状的临床确诊（曾患）百日咳患者队列以及一个荷兰人群队列中，对候选基因MBL2、IL17A、TNFα、VDR和IL10中的单核苷酸多态性（SNP）进行了基因分型。在五个基因中所研究的七个SNP里，维生素D受体（VDR）基因（rs10735810）中的一个多态性与百日咳相关。与对照人群队列相比，VDR主要等位基因及其纯合基因型在有症状百日咳患者队列中更为常见。有趣的是，VDR主要等位基因也与报告的百日咳症状持续时间相关。维生素D3（VD3）和VDR是免疫激活的重要调节因子。总之，这些发现表明VDR基因中的多态性可能影响免疫激活以及百日咳博德特氏菌感染的临床结局。
