P-selectin genotype is associated with the development of cancer cachexia.
P-selectin genotype is associated with the development of cancer cachexia.
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P-选择素基因型与癌症恶病质的发生有关。
DOI：
10.1002/emmm.201200231
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发表时间：
2012
影响因子：
11.1
通讯作者：
Skorpen,F
中科院分区：
文献类型：
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作者：
Tan,BenjaminHL;Fladvad,Torill;Braun,TheodoreP;Vigano,Antonio;Strasser,Florian;Deans,DAChristopher;Skipworth,RichardJE;Solheim,ToraS;Damaraju,Sambasivarao;Ross,JamesA;Kaasa,Stein;Marks,DanielL;Baracos,VickieE;Skorpen,F
恶病质的易患性可能部分是由于宿主基因型的相互作用。我们分析了80个基因中的129个单核苷酸多态性（SNP）与恶病质的相关性，这些基因基于体重减轻程度（>5，>10，>15%）以及全身炎症（C反应蛋白，>10 mg/l）存在下的体重减轻。对775名癌症患者进行了研究，并对独立招募的癌症患者队列（n= 101）进行了验证关联研究。C等位基因在发现研究中，发现rs6136（SELP）SNP的次要等位基因频率10.7%与体重减轻>10%相关，（比值比（OR）0.52; 95%可信区间（CI）0.29-0.93;p= 0.026）和验证研究（OR 0.09，95%CI 0.01- 0.98，p = 0.035）。在单独的研究中，在大鼠肿瘤诱导的恶病质或小鼠腹腔内注射脂多糖后，使用qPCR研究了肌肉萎缩基因表达的诱导。在两种模型中，发现P-选择素在肌肉中显著上调。P选择素在动物模型和恶病质癌症患者中的相关性鉴定支持其作为恶病质的风险因素/潜在介体。http://dx.doi.org/10.1002/emmm.201200232
The variable predisposition to cachexia may, in part, be due to the interaction of host genotype. We analyzed 129 single nucleotide polymorphisms (SNPs) in 80 genes for association with cachexia based on degree of weight loss (>5, >10, >15%) as well as weight loss in the presence of systemic inflammation (C‐reactive protein, >10 mg/l). 775 cancer patients were studied with a validation association study performed on an independently recruited cohort (n= 101) of cancer patients. The C allele (minor allele frequency 10.7%) of the rs6136 (SELP) SNP was found to be associated with weight loss >10% both in the discovery study (odds ratio (OR) 0.52; 95% confidence intervals (CI), 0.29–0.93;p= 0.026) and the validation study (OR 0.09, 95% CI 0.01–0.98,p= 0.035). In separate studies, induction of muscle atrophy gene expression was investigated using qPCR following either tumour‐induced cachexia in rats or intra‐peritoneal injection of lipopolysaccharide in mice. P‐selectin was found to be significantly upregulated in muscle in both models. Identification of P‐selectin as relevant in both animal models and in cachectic cancer patients supports this as a risk factor/potential mediator in cachexia.See accompanying article http://dx.doi.org/10.1002/emmm.201200232