Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl.
Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl.
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DOI：
10.1186/1744-8069-10-75
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发表时间：
2014-12-03
期刊：
影响因子：
3.3
通讯作者：
Ikeda K
中科院分区：
文献类型：
--
作者：
Ide S;Nishizawa D;Fukuda K;Kasai S;Hasegawa J;Hayashida M;Minami M;Ikeda K
P2 X7受体是腺苷5′-三磷酸门控阳离子通道P2 X家族的成员。最近的几项研究表明，这种受体参与了与疼痛和炎症相关的机制。然而，未知的是编码人类P2 X7受体的P2 RX 7基因的多态性是否影响阿片类药物的疼痛敏感性和镇痛作用。已知P2 RX 7基因具有高度多态性。因此，本研究在355名接受痛苦的口面部美容手术的日本患者中检查芬太尼敏感性和P2 RX 7基因多态性之间的关联。我们首先使用来自100名患者的基因组样本对P2 RX 7基因内和周围区域的55个已报道的单核苷酸多态性（SNP）进行了连锁不平衡（LD）分析。在我们的样本中，42个SNP是多态性的，总共观察到5个LD块，其中6个标签SNP（rs 2708092，rs 1180012，rs 1718125，rs 208293，rs 1718136和rs7132846）。因此，我们使用总共355个样本进一步分析了这些Tag SNP的基因型/单倍型与临床数据之间的关联。在基于基因型的关联研究中，只有rs 1718125 G > A SNP倾向于与术后24小时视觉模拟量表（VAS 24）上的较高疼痛评分相关。基于单倍型的关联研究表明，具有纯合子单倍型No.3（GTAAAC;估计频率：15.0%）的受试者在冷加压试验中表现出显著较高的冷痛敏感性和较低的芬太尼对急性冷痛的镇痛作用。相反，携带1号单倍型（ACGGAC;估计频率：24.5%）的受试者倾向于表现出较低的冷痛敏感性和较高的芬太尼镇痛作用。此外，纯合子单倍型2号（GCGGAC;估计频率：22.9%）的受试者表现出显着较低的VAS 24评分。冷痛敏感性和芬太尼镇痛作用与P2 RX 7基因的SNP和单倍型有关。具有rs 1718125 G>A SNP的患者倾向于显示较高的VAS 24评分。此外，从5′-侧翼区到外显子5的多态性的组合影响冷痛敏感性和阿片类药物对急性冷痛的镇痛作用。目前的研究结果揭示了P2 RX 7基因多态性参与幼稚冷痛敏感性和芬太尼的镇痛作用。本文的在线版本（doi：10.1186/1744-8069-10-75）包含补充材料，可供授权用户使用。
The P2X7 receptor is a member of the P2X family of adenosine 5′-triphosphate-gated cation channels. Several recent studies have demonstrated that this receptor is involved in mechanisms related to pain and inflammation. However, unknown is whether polymorphisms of the P2RX7 gene that encodes the human P2X7 receptor influence pain sensitivity and analgesic effects of opioids. The P2RX7 gene is known to be highly polymorphic. Thus, the present study examined associations between fentanyl sensitivity and polymorphisms in the P2RX7 gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery. We first conducted linkage disequilibrium (LD) analyses for 55 reported single-nucleotide polymorphisms (SNPs) in the region within and around the P2RX7 gene using genomic samples from 100 patients. In our samples, 42 SNPs were polymorphic, and a total of five LD blocks with six Tag SNPs (rs2708092, rs1180012, rs1718125, rs208293, rs1718136, and rs7132846) were observed. Thus, we further analyzed associations between genotypes/haplotypes of these Tag SNPs and clinical data using a total of 355 samples. In the genotype-based association study, only the rs1718125 G > A SNP tended to be associated with higher pain scores on a visual analog scale 24 h after surgery (VAS24). The haplotype-based association study showed that subjects with homozygous haplotype No.3 (GTAAAC; estimated frequency: 15.0%) exhibited significantly higher cold pain sensitivity and lower analgesic effects of fentanyl for acute cold pain in the cold pressor test. Conversely, subjects who carried haplotype No.1 (ACGGAC; estimated frequency: 24.5%) tended to exhibit lower cold pain sensitivity and higher analgesic effects of fentanyl. Furthermore, subjects with homozygous haplotype No.2 (GCGGAC; estimated frequency: 22.9%) exhibited significantly lower VAS24 scores. Cold pain sensitivity and analgesic effects of fentanyl were related to the SNP and haplotypes of the P2RX7 gene. The patients with the rs1718125 G>A SNP tended to show higher VAS24 scores. Moreover, the combination of polymorphisms from the 5′-flanking region to exon 5 recessively affected cold pain sensitivity and analgesic effects of opioids for acute cold pain. The present findings shed light on the involvement of P2RX7 gene polymorphisms in naive cold pain sensitivity and analgesic effects of fentanyl. The online version of this article (doi:10.1186/1744-8069-10-75) contains supplementary material, which is available to authorized users.
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DOI：
10.1523/jneurosci.3295-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark AK;Staniland AA;Marchand F;Kaan TK;McMahon SB;Malcangio M
通讯作者：
Malcangio M
P2X7 受体介导的 IL-18/IL-18R 信号转导在吗啡耐受中的作用：大鼠脊髓中的多个胶质神经元对话
影响因子：
4
作者：
Chen, Meng-Ling;Cao, Hong;Zhao, Zhi-Qi
通讯作者：
Zhao, Zhi-Qi
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
4.8
作者：
Feng, Ying-Hong;Li, Xin;Gorodeski, George I.
通讯作者：
Gorodeski, George I.
影响因子：
7.4
作者：
Bisgaard, T;Klarskov, B;Kehlet, H
通讯作者：
Kehlet, H