Department of Medicine, Clinical Epidemiology, and Biostatistics, McMaster University, Hamilton, Ontario.
J Infect Dis. 2011 Oct 1;204(7):1031-7. doi: 10.1093/infdis/jir493.
To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10(-5); odds ratio [OR], 0.68 [95% confidence interval {CI}, .56-.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10(-5); OR, 1.47 [95% CI, 1.21-1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10(-4); OR, 0.69 [95% CI, .56-.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease.
为了确定易患西尼罗河病毒感染后神经并发症的遗传因素，我们对 560 例神经侵袭性病例患者和 950 例对照患者进行了分析，共检测了 13371 个主要是非同义单核苷酸多态性（SNP）。基于统计学意义的前 3 个 SNP 也存在于具有生物学合理性的基因中：RFC1（复制因子 C1）中的 rs2066786（P=1.88×10(-5)；比值比[OR]，0.68[95%置信区间{CI}，0.56-0.81]）；SCN1A（神经元型钠离子通道 Iα亚单位）中的 rs2298771（P=5.87×10(-5)；OR，1.47[95% CI，1.21-1.77]）；以及 ANPEP（天冬氨酰基脯氨酰基肽酶）中的 rs25651（P=1.44×10(-4)；OR，0.69[95% CI，0.56-0.83]）。在另外 264 例病例患者和 296 例对照患者的独立样本中对这些 SNP 进行进一步基因分型，结果在复制队列中无显著意义；联合显著性如下：rs2066786，P=0.0022；rs2298771，P=0.005；rs25651，P=0.042。因此，我们主要使用非同义变体，并未发现与神经侵袭性疾病相关的遗传变异。
