Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Kidney Int. 2013 Dec;84(6):1207-13. doi: 10.1038/ki.2013.173. Epub 2013 May 15.
Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.
个体如果同时感染 HIV 和两种载脂蛋白 L1 基因（APOL1）风险变异体，通常会发展为肾病。在这里，我们通过定量聚合酶链反应评估载脂蛋白 L1 基因型以及尿液 JC 和 BK 多瘤病毒和血浆 HHV6 和 CMV 的存在，来测试非 HIV 病毒感染是否通过与 APOL1 的相互作用影响肾病风险。我们使用线性和非线性混合模型分析了 300 个来自非相关和相关的一级亲属的非洲裔美国人的样本，这些亲属患有非糖尿病性肾病，以考虑家族关系。评估的四个组是载脂蛋白 L1 零/一个与两个风险等位基因，有无肾病。分别在 90 名和 29 名患者中检测到尿 JCV 和 BKV，而 HHV6 和 CMV 则很少见。调整家族肾病发病年龄、性别和祖源后，尿液中 JCV 基因组 DNA 的存在和 APOL1 风险等位基因与血清胱抑素 C 升高、蛋白尿（白蛋白与肌酐比值超过 30mg/g）和肾病（定义为 eGFR 低于 60ml/min/1.73m²和/或蛋白尿）呈显著负相关在加性（APOL1 加 JCV）模型中。BK 病毒尿症与肾病无关。因此，APOL1 相关肾病风险增加的非裔美国人（两种 APOL1 风险变异体）如果存在 JC 病毒尿症，其肾病患病率较低，这表明 JCV 与 APOL1 基因型的相互作用可能影响肾病风险。
