Department of Anesthesiology, First Affiliated Hospital of Jiamusi University, Jiamusi, China.
Eur Rev Med Pharmacol Sci. 2020 May;24(9):5046-5052. doi: 10.26355/eurrev_202005_21197.
To investigate the correlations of analgesic dosage of morphine with solute carrier family 6 member 4 (SLC6A4) gene polymorphisms in patients with lung cancer.
A total of 200 lung cancer patients without cancer pain were selected as painless group, and another 200 lung cancer patients with cancer pain as cancer pain group. Visual Analogue Scale (VAS) was applied to grade the pain, the patients in cancer pain group were treated with morphine, and the dosage of morphine within 24 h was recorded. Then, the genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood of the research subjects, and the polymorphisms rs1042173 and rs7224199 of SLC6A4 gene were detected.
There was a difference in the genotype distribution of SLC6A4 gene rs7224199 between painless group and cancer pain group (p=0.004), and the frequency of GG genotype was remarkably higher in cancer pain group [75 (0.375)]. The frequency of heterozygous model AC of rs1042173 and recessive model GT + TT of rs7224199 in cancer pain group was evidently lower than that in painless group (p=0.048, p=0.043). Besides, the lung cancer patients in cancer pain group had markedly lower frequency of AG haplotype (p=0.000), but notably higher frequency of AT (p=0.000) and CG (p=0.000) haplotypes of SLC6A4 gene rs1042173 and rs7224199 than those in painless group. No significant differences in genotypes of SLC6A4 gene rs1042173 (p=0.241) and rs7224199 (p=0.316) were detected among the degrees of cancer pain in cancer pain group. The analgesic dosage of morphine for the lung cancer patients was prominently correlated with the genotypes of SLC6A4 gene rs1042173 in cancer pain group. Moreover, in cancer pain group, there were significant differences in the dosage within 24 h (p=0.025), at 24 h after weight correction (p=0.001) and at 24 h after correction of weight and body surface area (p=0.000) among the genotypes, and the morphine dosage for the patients with CC genotype was significantly lower. Furthermore, the morphine dosage within 24 h (p=0.047), at 24 h after weight correction (p=0.042) and at 24 h after correction of weight and body surface area (p=0.031) were distinctly associated with the haplotypes of SLC6A4 gene in cancer pain group, of which the patients with CT haplotype were administered with a remarkably lower morphine dosage.
The morphine dosage for analgesia has significant correlations with SLC6A4 gene polymorphisms in patients with lung cancer.
探讨肺癌患者吗啡镇痛剂量与溶质载体家族 6 成员 4（SLC6A4）基因多态性的相关性。
选择 200 例无癌痛的肺癌患者作为无痛组，200 例有癌痛的肺癌患者作为癌痛组。采用视觉模拟评分（VAS）对疼痛程度进行分级，癌痛组患者给予吗啡治疗，记录 24 h 内吗啡的用量。然后，从研究对象外周血中提取基因组脱氧核糖核酸（DNA），检测 SLC6A4 基因 rs1042173 和 rs7224199 多态性。
无痛组与癌痛组 SLC6A4 基因 rs7224199 的基因型分布存在差异（p=0.004），癌痛组 GG 基因型频率明显较高[75（0.375）]。rs1042173 的杂合模型 AC 和 rs7224199 的隐性模型 GT+TT 在癌痛组的频率明显低于无痛组（p=0.048，p=0.043）。此外，癌痛组肺癌患者 SLC6A4 基因 rs1042173 和 rs7224199 的 AG 单倍型频率明显较低（p=0.000），但 AT（p=0.000）和 CG（p=0.000）单倍型频率明显较高。癌痛组 SLC6A4 基因 rs1042173（p=0.241）和 rs7224199（p=0.316）的基因型在癌痛程度之间无显著差异。在癌痛组中，吗啡镇痛剂量与 SLC6A4 基因 rs1042173 的基因型显著相关。此外，在癌痛组中，基因型之间 24 h 内（p=0.025）、体重校正后 24 h（p=0.001）和校正体重和体表面积后 24 h（p=0.000）的吗啡用量存在显著差异，CC 基因型患者的吗啡用量明显较低。此外，癌痛组中 24 h 内（p=0.047）、体重校正后 24 h（p=0.042）和校正体重和体表面积后 24 h（p=0.031）的吗啡用量与 SLC6A4 基因的单倍型明显相关，其中 CT 单倍型患者的吗啡用量明显较低。
肺癌患者的吗啡镇痛剂量与 SLC6A4 基因多态性显著相关。
