The Association Between APOL1 Risk Alleles and Longitudinal Kidney Function Differs by HIV Viral Suppression Status
The Association Between APOL1 Risk Alleles and Longitudinal Kidney Function Differs by HIV Viral Suppression Status
复制标题
DOI：
10.1093/cid/ciu765
复制
发表时间：
2015-02-15
影响因子：
11.8
通讯作者：
Kao, W. H. Linda
中科院分区：
文献类型：
--
作者：
Estrella, Michelle M.;Li, Man;Kao, W. H. Linda
背景现有数据表明，携带2个APOL 1风险等位基因拷贝的人类免疫缺陷病毒（HIV）感染的非裔美国人比非携带者有更大的肾脏疾病风险。我们试图确定HIV RNA抑制是否能减轻参与多中心AIDS队列研究的非裔美国人中APOL 1相关的肾功能下降。我们对HIV感染者进行了G1和G2风险等位基因和祖先信息标记的基因分型。混合效应模型用于估计肾小球滤过率（eGFR）下降的年速率，比较携带2（高风险）与0-1风险等位基因（低风险）的男性。使用交互作用项和分层分析评估了HIV抑制状态（定义为随访时间内HIV 1型RNA水平> 90%）对疗效的影响。在这项研究中纳入的333名非洲裔美国男性中，54名（16%）携带APOL 1高风险基因型。在病毒载量未受抑制的HIV感染男性中，高风险基因型男性的eGFR年下降速度比低风险基因型男性快2.42 mL/min/1.73 m2（95%置信区间[CI]，-3.52至-1.32）。这种关联与年龄、共病、基线eGFR、血统和HIV相关因素无关。相比之下，在持续病毒抑制的男性中，APOL 1基因型的下降率相似（-0.16 mL/min/1.73 m2/年; 95%CI，-0.59至0.27;相互作用P
Background. Existing data suggest that human immunodeficiency virus (HIV)-infected African Americans carrying 2 copies of the APOL1 risk alleles have greater risk of kidney disease than noncarriers. We sought to determine whether HIV RNA suppression mitigates APOL1-related kidney function decline among African Americans enrolled in the Multicenter AIDS Cohort Study.Methods. We genotyped HIV-infected men for the G1 and G2 risk alleles and ancestry informative markers. Mixed-effects models were used to estimate the annual rate of estimated glomerular filtration rate (eGFR) decline, comparing men carrying 2 (high-risk) vs 0-1 risk allele (low-risk). Effect modification by HIV suppression status (defined as HIV type 1 RNA level 90% of follow-up time) was evaluated using interaction terms and stratified analyses.Results. Of the 333 African American men included in this study, 54 (16%) carried the APOL1 high-risk genotype. Among HIV-infected men with unsuppressed viral loads, those with the high-risk genotype had a 2.42 mL/minute/1.73 m(2) (95% confidence interval [CI], -3.52 to -1.32) faster annual eGFR decline than men with the low-risk genotype. This association was independent of age, comorbid conditions, baseline eGFR, ancestry, and HIV-related factors. In contrast, the rate of decline was similar by APOL1 genotype among men with sustained viral suppression (-0.16 mL/minute/1.73 m(2)/year; 95% CI, -.59 to .27; P for interaction