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ASTN2 基因 rs958804 和 rs7858836 单核苷酸多态性对腹腔镜结肠切除术和下颌矢状劈开截骨术后患者疼痛相关表型的影响。

Effects of rs958804 and rs7858836 single-nucleotide polymorphisms of the ASTN2 gene on pain-related phenotypes in patients who underwent laparoscopic colectomy and mandibular sagittal split ramus osteotomy.

机构信息

Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

出版信息

Neuropsychopharmacol Rep. 2021 Mar;41(1):82-90. doi: 10.1002/npr2.12159. Epub 2021 Jan 21.

Abstract

BACKGROUND

Opioids are widely used as effective analgesics, but opioid sensitivity varies widely among individuals. The underlying genetic and nongenetic factors are not fully understood. Based on the results of our previous genome-wide association study, we investigated the effects of single nucleotide polymorphisms (SNPs) of the astrotactin 2 (ASTN2) gene on pain-related phenotypes in surgical patients.

METHODS

We investigated the effects of two SNPs, rs958804 T/C and rs7858836 C/T, of the ASTN2 gene on eight and seven pain-related phenotypes in 350 patients who underwent laparoscopic colectomy (LAC) and 358 patients who underwent mandibular sagittal split ramus osteotomy (SSRO), respectively. In both surgical groups, intravenous fentanyl patient-controlled analgesia (PCA) was used for postoperative analgesia, and 24-hour postoperative PCA fentanyl use was the primary endpoint.

RESULTS

The association analyses among the two SNPs and pain-related traits showed that 24-hour fentanyl use was significantly associated with the two SNP genotypes in both surgical groups. The Mann-Whitney test showed that 24-hour fentanyl use was lower in patients with the C allele than in patients with the TT genotype of the rs958804 T/C SNP (P = .0019 and .0200 in LAC and SSRO patients, respectively), and it was lower in patients with the T allele than in patients with the CC genotype of the rs7858836 C/T SNP (P = .0017 and .0098 in LAC and SSRO patients, respectively).

CONCLUSION

The two SNPs of the ASTN2 gene were consistently associated with fentanyl requirements after two different types of surgery. These findings may contribute to personalized pain control.

摘要

背景

阿斯特丁 2(ASTN2)基因的单核苷酸多态性(SNP)对手术患者的疼痛相关表型的影响

方法

我们研究了 ASTN2 基因的两个 SNP(rs958804 T/C 和 rs7858836 C/T)对 350 例接受腹腔镜结肠切除术(LAC)和 358 例接受下颌矢状劈开截骨术(SSRO)患者的 8 种和 7 种疼痛相关表型的影响。在两组手术中,均采用静脉注射芬太尼患者自控镇痛(PCA)进行术后镇痛,24 小时术后 PCA 芬太尼用量为主要终点。

结果

rs958804 T/C 和 rs7858836 C/T 两个 SNP 与疼痛相关特征的关联分析表明,两种 SNP 基因型与两种手术的 24 小时芬太尼使用均显著相关。Mann-Whitney 检验显示,与 rs958804 T/C SNP 的 TT 基因型相比,C 等位基因患者的 24 小时芬太尼用量较低(P=0.0019 和 0.0200,分别为 LAC 和 SSRO 患者),与 rs7858836 C/T SNP 的 CC 基因型相比,T 等位基因患者的 24 小时芬太尼用量较低(P=0.0017 和 0.0098,分别为 LAC 和 SSRO 患者)。

结论

ASTN2 基因的两个 SNP 与两种不同类型手术后芬太尼的需求一致相关。这些发现可能有助于实现个性化疼痛控制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e173/8182957/b0e2128152e2/NPR2-41-82-g001.jpg

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