Bougnères Pierre, Le Fur Sophie, Valtat Sophie, Kamatani Yoichiro, Lathrop Mark, Valleron Alain-Jacques
Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, AP-HP, Le Kremlin Bicêtre, France.
Inserm U1169, Paris Sud University, Le Kremlin Bicêtre, France.
PLoS One. 2017 Feb 2;12(2):e0170658. doi: 10.1371/journal.pone.0170658. eCollection 2017.
The "hygiene hypothesis" postulates that reduced exposure to infections favours the development of autoimmunity and childhood type 1 diabetes (T1D). But on the other side, viruses, notably enteroviruses, are suspected to trigger T1D. The assessment of the possible relationships between infections and T1D still defies the classical tools of epidemiology. We report the methods and results of a geographical approach that maps the addresses of patients to a communicable diseases surveillance database. We mapped the addresses of patients at birth, infancy and T1D diagnosis to the weekly estimates of the regional incidences of 5 frequent communicable diseases routinely collected since 1984 by the French Sentinel network. The pre-diagnostic infectious environment of 3548 patients with T1D diagnosed between 0.5 and 15 years was compared to those of 100 series of age-matched "virtual controls" drawn randomly on the map. Associations were classified as "suggestive" (summer diarrhea, SD, and varicella, V) when p< 0.05, or "significant" (influenza-like infections, ILI) when they passed the Bonferroni correction for FDR. Exposure to ILI and SD were associated with T1D risk, while V seemed protective. In the subset of 2521 patients for which we had genome wide data, we used a case-only approach to search for interactions between SNPs and the infectious environment as defined by the Sentinel database. Two SNPs, rs116624278 and rs77232854, showed significant interaction with exposure to V between 1 and 3 years of life. The infectious associations found should be taken as possible markers of patients' environment, not as direct causative factors of T1D. They require replication in other populations. The increasing public availability of geographical environmental databases will expand the present approach to map thousands of environmental factors to the lifeline of patients affected by various diseases.
“卫生假说”假定，减少感染暴露有利于自身免疫性疾病和儿童1型糖尿病（T1D）的发展。但另一方面，病毒，尤其是肠道病毒，被怀疑会引发T1D。对感染与T1D之间可能存在的关系进行评估，仍超出了传统流行病学工具的范畴。我们报告了一种地理方法的方法和结果，该方法将患者地址映射到传染病监测数据库。我们将患者出生时、婴儿期及T1D诊断时的地址，映射到自1984年以来由法国哨点网络定期收集的5种常见传染病的区域发病率的每周估计值。将3548例0.5至15岁确诊的T1D患者的诊断前感染环境，与在地图上随机抽取的100组年龄匹配的“虚拟对照”的感染环境进行比较。当p<0.05时，关联被分类为“提示性”（夏季腹泻，SD，和水痘，V），或当它们通过FDR的Bonferroni校正时为“显著”（流感样感染，ILI）。暴露于ILI和SD与T1D风险相关，而V似乎具有保护作用。在我们拥有全基因组数据的2521例患者子集中，我们采用仅病例研究方法，寻找单核苷酸多态性（SNP）与哨点数据库定义的感染环境之间的相互作用。两个SNP，rs116624278和rs77232854，显示出与1至3岁时暴露于V有显著相互作用。所发现的感染关联应被视为患者环境的可能标志物，而非T1D的直接致病因素。它们需要在其他人群中进行重复验证。地理环境数据库的公众可获取性不断增加，将扩展目前的方法，以将数千种环境因素映射到受各种疾病影响患者的生命线上。
