Genome-wide association study of high-sensitivity C-reactive protein, D-dimer, and interleukin-6 levels in multiethnic HIV+ cohorts.
Genome-wide association study of high-sensitivity C-reactive protein, D-dimer, and interleukin-6 levels in multiethnic HIV+ cohorts.
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DOI：
10.1097/qad.0000000000002738
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发表时间：
2021-02-02
期刊：
影响因子：
--
通讯作者：
ESPRIT, SMART and START Study Groups
中科院分区：
文献类型：
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作者：
Sherman BT;Hu X;Singh K;Haine L;Rupert AW;Neaton JD;Lundgren JD;Imamichi T;Chang W;Lane HC;ESPRIT, SMART and START Study Groups
白细胞介素-6（IL-6）、D-二聚体和C-反应蛋白（hsCRP）水平升高与HIV感染者（PLWH）共病发病率和死亡率增加相关。先前的研究表明，一般人群中这些生物标志物升高的遗传基础。研究的目的是确定这些生物标志物的遗传基础PLWH。在三项HIV治疗试验中，测定了7768名参与者的hsCRP、D-二聚体、IL-6和单核苷酸多态性（SNP）的基线水平。在每项试验中，对来自三个种族组[非洲人（AFR）、美国混血儿（AMR）、欧洲人（EUR）]的样本中的每种生物标志物进行单变量分析，包括与生物标志物水平相关的协变量。对于每个种族组，将试验结果汇总，然后进一步汇总种族结果。跨种族分析确定了三个，两个和一个已知的基因座与hsCRP，D-二聚体，IL-6水平，分别和两个新的基因座，FGB和GCNT 1，与D-二聚体水平。主要SNP在不同种族中表现出相似的效果。此外，还发现了三个新的种族特异性基因座：AFR中与D-二聚体相关的CATSPERG和AFR和AMR中分别与IL-6相关的PROX 1-AS 1和TRAPPC 9。从三项研究中确定了PLWH中与三种生物标志物水平相关的11个基因座，包括一般人群中已知的6个基因座和与D-二聚体和IL-6水平相关的5个新基因座。这些发现支持宿主遗传学可能部分导致PLWH慢性炎症的假设，并有助于确定干预严重非艾滋病并发症的潜在靶点。
Elevated levels of interleukin-6 (IL-6), D-dimer, and C-reactive protein (hsCRP) are associated with increased incidence of comorbid disease and mortality among people living with HIV (PLWH). Prior studies suggest a genetic basis for these biomarker elevations in the general population. The study objectives are to identify the genetic basis for these biomarkers among PLWH. Baseline levels of hsCRP, D-dimer, and IL-6, and single nucleotide polymorphisms (SNPs) were determined for 7768 participants in three HIV treatment trials. Single variant analysis was performed for each biomarker on samples from each of three ethnic groups [African (AFR), Admixed American (AMR), European (EUR)] within each trial including covariates relevant to biomarker levels. For each ethnic group, the results were pooled across trials, then further pooled across ethnicities. The transethnic analysis identified three, two, and one known loci associated with hsCRP, D-dimer, and IL-6 levels, respectively, and two novel loci, FGB and GCNT1, associated with D-dimer levels. Lead SNPs exhibited similar effects across ethnicities. Additionally, three novel, ethnic-specific loci were identified: CATSPERG associated with D-dimer in AFR and PROX1-AS1 and TRAPPC9 associated with IL-6 in AFR and AMR, respectively. Eleven loci associated with three biomarker levels were identified in PLWH from the three studies including six loci known in the general population and five novel loci associated with D-dimer and IL-6 levels. These findings support the hypothesis that host genetics may partially contribute to chronic inflammation in PLWH and help to identify potential targets for intervention of serious non-AIDS complications.