Norwegian Institute of Public Health, Oslo, Norway.
PLoS One. 2011;6(11):e27781. doi: 10.1371/journal.pone.0027781. Epub 2011 Nov 14.
Interferon induced with helicase C domain 1 (IFIH1) senses and initiates antiviral activity against enteroviruses. Genetic variants of IFIH1, one common and four rare SNPs have been associated with lower risk for type 1 diabetes. Our aim was to test whether these type 1 diabetes-associated IFIH1 polymorphisms are associated with the occurrence of enterovirus infection in the gut of healthy children, or influence the lack of association between gut enterovirus infection and islet autoimmunity.After testing of 46,939 Norwegian newborns, 421 children carrying the high risk genotype for type 1 diabetes (HLA-DR4-DQ8/DR3-DQ2) as well as 375 children without this genotype were included for monthly fecal collections from 3 to 35 months of age, and genotyped for the IFIH1 polymorphisms. A total of 7,793 fecal samples were tested for presence of enterovirus RNA using real time reverse transcriptase PCR.We found no association with frequency of enterovirus in the gut for the common IFIH1 polymorphism rs1990760, or either of the rare variants of rs35744605, rs35667974, rs35337543, while the enterovirus prevalence marginally differed in samples from the 8 carriers of a rare allele of rs35732034 (26.1%, 18/69 samples) as compared to wild-type homozygotes (12.4%, 955/7724 samples); odds ratio 2.5, p = 0.06. The association was stronger when infections were restricted to those with high viral loads (odds ratio 3.3, 95% CI 1.3-8.4, p = 0.01). The lack of association between enterovirus frequency and islet autoimmunity reported in our previous study was not materially influenced by the IFIH1 SNPs.We conclude that the type 1 diabetes-associated IFIH1 polymorphisms have no, or only minor influence on the occurrence, quantity or duration of enterovirus infection in the gut. Its effect on the risk of diabetes is likely to lie elsewhere in the pathogenic process than in the modification of gut infection.
IFIH1 是一种具有螺旋酶 C 结构域的干扰素诱导蛋白，能够识别并启动针对肠道病毒的抗病毒活性。IFIH1 的一种常见和四种罕见单核苷酸多态性（SNP）与 1 型糖尿病的低风险相关。我们的目的是检测这些与 1 型糖尿病相关的 IFIG1 多态性是否与健康儿童肠道中肠道病毒感染的发生有关，或者是否影响肠道病毒感染与胰岛自身免疫之间缺乏关联。
在对 46939 名挪威新生儿进行检测后，我们纳入了 421 名携带 1 型糖尿病高危基因型（HLA-DR4-DQ8/DR3-DQ2）的儿童以及 375 名无此基因型的儿童，从 3 至 35 月龄每月采集粪便样本，并对 IFIG1 多态性进行基因分型。使用实时逆转录聚合酶链反应检测 7793 份粪便样本中肠道病毒 RNA 的存在情况。
我们发现常见的 IFIG1 多态性 rs1990760 与肠道内肠道病毒的频率无关，或者罕见的 rs35744605、rs35667974、rs35337543 变异体也与肠道病毒的流行无关，而 rs35732034 罕见等位基因携带者的粪便样本中肠道病毒的流行率（26.1%，18/69 份样本）与野生型纯合子（12.4%，955/7724 份样本）相比则略有不同；比值比 2.5，p=0.06。当感染限于高病毒载量时，相关性更强（比值比 3.3，95%CI 1.3-8.4，p=0.01）。我们之前的研究表明肠道病毒频率与胰岛自身免疫之间缺乏关联，而 IFIH1SNP 并没有明显影响这一关联。
综上所述，与 1 型糖尿病相关的 IFIG1 多态性对肠道病毒感染的发生、数量或持续时间没有影响，或者只有轻微影响。其对糖尿病风险的影响可能位于发病机制的其他部位，而不是肠道感染的改变。
