Vascular endothelial growth factor A polymorphism and risk of Kaposi's sarcoma herpesvirus viremia in kidney allograft recipients

Vascular endothelial growth factor A polymorphism and risk of Kaposi's sarcoma herpesvirus viremia in kidney allograft recipients
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DOI:
10.1111/tid.12277
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发表时间:
2014-10-01
影响因子:
2.6
通讯作者:
Al-Ali, A. K.
Al-Ali, A. K.
中科院分区:
医学4区
文献类型:
--
作者:
Alkharsah, K. R.;Alzahrani, A. J.;Al-Ali, A. K.

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背景卡波西肉瘤疱疹病毒(KSHV)在包括同种异体移植受体在内的免疫功能低下患者中引起卡波西肉瘤(KS)、原发性渗出性淋巴瘤和多中心Castleman病。已发现血液中KSHV DNA的检测以及宿主遗传多态性与KS风险增加相关。我们研究了在沙特阿拉伯肾移植受者(KTR)中血管内皮生长因子A(VEGFA)基因区的单核苷酸多态性(SNPs)与KSHV病毒血症之间的关联。KSHV病毒血症通过实时聚合酶链反应(PCR)确定。在VEGFA区域的SNPs基因分型进行PCR和直接测序,以及通过限制性片段长度多态性.ResultsKSHV DNA检测在28.9%(n=44)的研究人群。VEGFA基因启动子区C172 A位点A等位基因与KSHV病毒血症相关(OR =4.8,P=0.005)。此外,在位置C+405 G在5-非翻译区G等位基因与KSHV病毒血症的女性,但不与男性(OR=3.98,P=0.004)。本研究的一个局限性是,该结果只能预测肾移植后6个月的患者,需要在另一个更大样本量的队列中进行验证。
BackgroundKaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease in immunocompromised patients including allograft recipients. Detection of KSHV DNA in blood, as well as host genetic polymorphisms has been found to be associated with an increased risk for KS. We investigated an association between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) gene region and KSHV viremia in kidney transplant recipients (KTR) in Saudi Arabia.MethodsIn total, 152 KTR who have survived kidney transplantation for at least 6months were included in the study. KSHV viremia was determined by real-time polymerase chain reaction (PCR). Genotyping of SNPs in the VEGFA region was performed by PCR and direct sequencing, as well as by restriction fragment length polymorphism.ResultsKSHV DNA was detected in 28.9% (n=44) of the study population. The A-allele at position C172A VEGFA gene promoter region was found to be associated with KSHV viremia (odd ratio [OR]=4.8, P=0.005). In addition, the G-allele at position C+405G in the 5-untranslated region was associated with KSHV viremia in women, but not in men (OR=3.98, P=0.004).ConclusionsOur results suggest an association of VEGFA polymorphisms with KSHV viremia among KTR in this study population. A limitation of our study is that the results can only be predicated for patients 6months after kidney transplantation and should be validated in another cohort with larger sample size.