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TLR3、IL10 和 CD209 基因多态性影响肾移植后 BK 多瘤病毒感染的风险。

Genetic polymorphisms in TLR3, IL10 and CD209 influence the risk of BK polyomavirus infection after kidney transplantation.

机构信息

Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Centro de Actividades Ambulatorias, 6ª planta, Bloque D. Avda. de Córdoba, s/n, 28041, Madrid, Spain.

Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas, Madrid, Spain.

出版信息

Sci Rep. 2022 Jul 5;12(1):11338. doi: 10.1038/s41598-022-15406-0.

Abstract

Genetic determinants of BK polyomavirus infection after kidney transplantation remain poorly investigated. We assessed the potential impact of 13 different single nucleotide polymorphisms within genes mainly involved in innate immune responses on the risk of BKPyV viremia in 204 KT recipients. After a median follow-up of 1121.5 days, the cumulative incidence of any-level BKPyV viremia was 24.5% (50/204). There was a significant association between the minor T allele of TLR3 (rs3775291) SNP and the development of BKPyV viremia (adjusted hazard ratio [aHR]: 2.16; 95% confidence interval [CI]: 1.08-4.30; P value = 0.029), whereas the minor G allele of CD209 (rs4804803) SNP exerted a protective role (aHR: 0.54; 95% CI: 0.29-1.00; P value = 0.050). A higher incidence of BKPyV viremia was also observed for the minor G allele of IL10 (rs1800872) SNP, although the absence of BKPyV events among homozygotes for the reference allele prevented multivariable analysis. The BKPyV viremia-free survival rate decreased with the increasing number of unfavorable genotypes (100% [no unfavorable genotypes], 85.4% [1 genotype], 70.9% [2 genotypes], 52.5% [3 genotypes]; P value = 0.008). In conclusion, SNPs in TLR3, CD209 and IL10 genes play a role in modulating the susceptibility to any-level BKPyV viremia among KT recipients.

摘要

肾移植后 BK 多瘤病毒感染的遗传决定因素仍未得到充分研究。我们评估了主要参与固有免疫反应的基因中的 13 个不同单核苷酸多态性在 204 例肾移植受者 BKPyV 血症风险中的潜在影响。中位随访 1121.5 天后,任何程度的 BKPyV 血症累积发生率为 24.5%(50/204)。TLR3(rs3775291)SNP 的次要 T 等位基因与 BKPyV 血症的发生存在显著相关性(调整后的危险比[aHR]:2.16;95%置信区间[CI]:1.08-4.30;P 值=0.029),而 CD209(rs4804803)SNP 的次要 G 等位基因则发挥保护作用(aHR:0.54;95%CI:0.29-1.00;P 值=0.050)。IL10(rs1800872)SNP 的次要 G 等位基因也观察到 BKPyV 血症的发生率较高,尽管由于参考等位基因的纯合子中没有 BKPyV 事件,因此无法进行多变量分析。随着不利基因型数量的增加,BKPyV 血症无复发生存率降低(100%[无不利基因型]、85.4%[1 种基因型]、70.9%[2 种基因型]、52.5%[3 种基因型];P 值=0.008)。总之,TLR3、CD209 和 IL10 基因中的 SNP 在调节肾移植受者任何程度的 BKPyV 血症易感性方面发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88b8/9256743/08fc7193ff71/41598_2022_15406_Fig1_HTML.jpg

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