Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain.
Rheumatology (Oxford). 2022 Aug 3;61(8):3180-3191. doi: 10.1093/rheumatology/keab911.
It is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA), and that pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate genes) and the gene-gene, gene-PA and gene-sedentary behaviour interactions with pain and pain-related cognitions in women with FM.
Saliva samples from 274 women with FM [mean (s.d.) age 51.7 (7.7) years] were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed.
The rs6311 and rs6313 polymorphisms (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor μ gene, OPRM1) was related to pain catastrophizing. Five gene-behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of FM symptoms (codominant model, P-value 0.032).
The HTR2A gene (individually), COMT and OPRM1 gene-gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene-sedentary behaviour interaction to pain and pain catastrophizing in women with FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.
众所周知，疼痛的体验既受遗传易感性的影响，也受体育活动（PA）等环境因素的影响，疼痛相关认知也很重要。因此，本研究的目的是测试 64 个多态性（34 个候选基因）以及基因-基因、基因-PA 和基因-久坐行为相互作用与纤维肌痛（FM）女性疼痛和疼痛相关认知的关系。
从 274 名 FM 女性（平均[标准差]年龄 51.7[7.7]岁）采集唾液样本，用于提取 DNA。我们通过加速度计测量一周的 PA 和久坐行为，通过测痛计和问卷测量疼痛，通过问卷测量疼痛相关认知。为了评估结果的稳健性，还进行了荟萃分析。
rs6311 和 rs6313 多态性（5-羟色胺受体 2A，HTR2A）单独与测痛计评分相关。rs4818（儿茶酚-O-甲基转移酶，COMT）和 rs1799971（阿片受体μ基因，OPRM1）的相互作用与疼痛灾难化有关。有 5 个基因-行为相互作用是显著的：与 rs1383914（肾上腺素能受体α 1A，ADRA1A）、rs6860（带电荷多泡体蛋白 1A，CHMP1A）、rs4680（COMT）、rs165599（COMT）和 rs12994338（SCN9A）的久坐行为相互作用与 SF-36 身体疼痛子量表有关。此外，荟萃分析显示 rs4680（COMT）与 FM 症状严重程度之间存在关联（共显性模型，P 值为 0.032）。
HTR2A 基因（单独）、COMT 和 OPRM1 基因-基因相互作用以及久坐行为与 ADRA1A、CHMP1A、COMT 和 SCN9A 基因的相互作用与疼痛相关结果相关。总之，本研究的结果表明遗传和基因-久坐行为相互作用对 FM 女性的疼痛和疼痛灾难化有一定的影响。未来的研究应探讨减少久坐行为是否对减轻有疼痛遗传易感性的女性的疼痛特别有益。
