他汀类药物相关性肌痛与血清素受体的生理基因组学关联

Physiogenomic association of statin-related myalgia to serotonin receptors.

作者信息

Ruaño Gualberto, Thompson Paul D, Windemuth Andreas, Seip Richard L, Dande Amit, Sorokin Alexey, Kocherla Mohan, Smith Andrew, Holford Theodore R, Wu Alan H B

机构信息

Genomas, Inc., 67 Jefferson Street, Hartford, Connecticut 06102, USA.

出版信息

Muscle Nerve. 2007 Sep;36(3):329-35. doi: 10.1002/mus.20871.

DOI:10.1002/mus.20871

PMID:17600820

Abstract

We employed physiogenomic analyses to investigate the relationship between myalgia and selected polymorphisms in serotonergic genes, based on their involvement with pain perception and transduction of nociceptive stimuli. We screened 195 hypercholesterolemic, statin-treated patients, all of whom received either atorvastatin, simvastatin, or pravastatin. Patients were classified as having no myalgia, probable myalgia, or definite myalgia, and assigned a myalgia score of 0, 0.5, or 1, respectively. Fourteen single nucleotide polymorphisms (SNPs) were selected from candidates within the 5-HT receptor gene families [5a-hydroxytryptamine receptor genes (HTR) 1D, 2A, 2C, 3A, 3B, 5A, 6, 7] and the serotonin transporter gene (SLC6A4). SNPs in the HTR3B and HTR7 genes, rs2276307 and rs1935349, respectively, were significantly associated with the myalgia score. Individual differences in pain perception and nociception related to specific serotonergic gene variants may affect the development of myalgia in statin-treated patients.

摘要

基于血清素能基因与疼痛感知及伤害性刺激转导的关联，我们采用生理基因组学分析来研究肌痛与血清素能基因中选定多态性之间的关系。我们筛选了195名接受他汀类药物治疗的高胆固醇血症患者，他们均服用阿托伐他汀、辛伐他汀或普伐他汀。患者被分类为无肌痛、可能有肌痛或确诊有肌痛，并分别给予肌痛评分为0、0.5或1。从5-羟色胺受体基因家族[5-羟色胺受体基因（HTR）1D、2A、2C、3A、3B、5A、6、7]和血清素转运体基因（SLC6A4）中的候选基因中选择了14个单核苷酸多态性（SNP）。HTR3B和HTR7基因中的SNP，即rs2276307和rs1935349，分别与肌痛评分显著相关。与特定血清素能基因变异相关的疼痛感知和伤害感受的个体差异可能会影响他汀类药物治疗患者肌痛的发生。