Identification of haplotype tag single nucleotide polymorphisms within the nuclear factor-κB family genes and their clinical relevance in patients with major trauma.
Identification of haplotype tag single nucleotide polymorphisms within the nuclear factor-κB family genes and their clinical relevance in patients with major trauma.
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核因子-κB家族基因内单倍型标签单核苷酸多态性的鉴定及其与重大创伤患者的临床相关性
DOI：
10.1186/s13054-015-0836-6
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发表时间：
2015-03-20
期刊：
影响因子：
--
通讯作者：
Jiang JX
中科院分区：
文献类型：
--
作者：
Pan W;Zhang AQ;Gu W;Gao JW;Du DY;Zhang LY;Zeng L;Du J;Wang HY;Jiang JX
核因子-κB（NF-κB）家族在危重患者脓毒症的发生发展中起重要作用。尽管在NF-κB家族基因中已经发现了几种单核苷酸多态性（SNP），但只有少数SNP得到了研究。共有753例严重钝性创伤患者纳入本研究。通过构建单倍型区组，从NF-κB家族基因（NF KB 1、NF KB 2、RELA、RELB和REL）中筛选标签SNPs（tSNPs）。采用焦磷酸测序法对NF-κB通路（包括NF KB 1、RELA和REL）中在先天免疫应答中起关键作用的基因进行SNP分型，并分析其与脓毒症和多器官功能障碍（MOD）综合征发生风险的关系。此外，rs 842647多态性与外周血白细胞响应细菌脂蛋白刺激产生肿瘤坏死因子α（TNF-α）的关系进行了分析。从NF-κB家族基因中筛选出8个SNP（rs 28362491、rs3774932、rs 4648068、rs7119750、rs 4803789、rs 12609547、rs 1560725和rs 842647）。在本研究队列中，所有这些都被证明是高频SNP。对经典NF-κB通路中的4个SNP（rs 28362491、rs 4648068、rs7119750和rs 842647）进行基因分型，其中rs 842647与脓毒症发病率和MOD评分相关。还观察到rs 842647 A等位基因与较低的TNF-α产生之间存在关联。rs 842647基因多态性可作为严重创伤患者发生脓毒症和MOD综合征的相关风险评估指标。本文的在线版本（doi：10.1186/s13054-015-0836-6）包含补充材料，可供授权用户使用。
Nuclear factor-κB (NF-κB) family plays an important role in the development of sepsis in critically ill patients. Although several single nucleotide polymorphisms (SNPs) have been identified in the NF-κB family genes, only a few SNPs have been studied. A total of 753 patients with major blunt trauma were included in this study. Tag SNPs (tSNPs) were selected from the NF-κB family genes (NFKB1, NFKB2, RELA, RELB and REL) through construction of haplotype blocks. The SNPs selected from genes within the canonical NF-κB pathway (including NFKB1, RELA and REL), which played a critical role in innate immune responses were genotyped using pyrosequencing method and analyzed in relation to the risk of development of sepsis and multiple organ dysfunction (MOD) syndrome. Moreover, the rs842647 polymorphism was analyzed in relation to tumor necrosis factor α (TNF-α) production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Eight SNPs (rs28362491, rs3774932, rs4648068, rs7119750, rs4803789, rs12609547, rs1560725 and rs842647) were selected from the NF-κB family genes. All of them were shown to be high-frequency SNPs in this study cohort. Four SNPs (rs28362491, rs4648068, rs7119750 and rs842647) within the canonical NF-κB pathway were genotyped, and rs842647 was associated with sepsis morbidity rate and MOD scores. An association was also observed between the rs842647 A allele and lower TNF-α production. rs842647 polymorphism might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma. The online version of this article (doi:10.1186/s13054-015-0836-6) contains supplementary material, which is available to authorized users.
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影响因子：
4.4
作者：
Perera, PY;Mayadas, TN;Vogel, SN
通讯作者：
Vogel, SN
DOI：
10.2174/187221311794474892
发表时间：
2011-01-01
影响因子：
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影响因子：
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作者：
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