HLA-DQ6 and ingestion of contaminated water: possible gene-environment interaction in an outbreak of leptospirosis
HLA-DQ6 and ingestion of contaminated water: possible gene-environment interaction in an outbreak of leptospirosis
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DOI：
10.1038/sj.gene.6364058
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发表时间：
2004-05-01
影响因子：
5
通讯作者：
McNicholl, J
中科院分区：
文献类型：
--
作者：
Lingappa, J;Kuffner, T;McNicholl, J
钩端螺旋体病是一种人畜共患病，可引起严重的多系统疾病。虽然宿主基因-环境相互作用可能会改变感染性疾病的易感性，包括钩端螺旋体病，但这还没有记录。在1998年的一次湖泊游泳铁人三项运动员钩端螺旋体病爆发调查中，吞咽湖水是疾病的危险因素。我们使用来自该调查的85名匿名血液样本采集者的基因组DNA，研究实验室确认的钩端螺旋体病与基因多态性（TNF-α等位基因和HLA-DRB 1和HLA-DQB 1的血清学定义的基因型）的相关性。HLA-DQ 6阳性的铁人三项运动员与DQ 6阴性的相比，实验室确诊的钩端螺旋体病的风险增加（OR = 2.8，P = 0.04）。DQ 6阳性者吞咽湖水的危险性最大（OR 8.46，P <0.001）。这是第一份关于影响钩端螺旋体病易感性的遗传风险因素的报告，也是第一份记录在案的影响传染病易感性的基因-环境相互作用（DQ 6和吞咽的水）。基于这些初步研究结果，我们假设超抗原在钩端螺旋体病中的作用，并强调暴发调查对了解传染病基因环境相互作用的重要性。
Leptospirosis is a zoonosis that can cause severe multisystem disease. While host gene-environment interactions likely modify infectious disease susceptibility, including for leptopsirosis, this has not been documented. In a 1998 leptospirosis outbreak investigation among triathletes in a lake swim, swallowing lake-water was a disease risk-factor. We used genomic DNA from 85 anonymized blood-sample remainders from that investigation to examine the association of laboratory-confirmed leptospirosis with gene polymorphisms (TNF-alpha alleles and serologically defined genotypes for HLA-DRB1 and HLA-DQB1). HLA-DQ6-positive triathletes had increased risk of laboratory-confirmed leptospirosis ( OR = 2.8, P = 0.04) compared to DQ6-negatives. DQ6-positive triathletes swallowing lake-water had greatest risk ( OR 8.46, Pless than or equal to0.001). This first report of a genetic risk-factor affecting susceptibility to leptospirosis is also the first documented gene - environment interaction (DQ6 and swallowed water) affecting infectious disease susceptibility. Based on these preliminary findings, we hypothesize a role for superantigens in leptospirosis and underscore the importance of outbreak investigations for understanding infectious disease gene environment interactions.