Department of Cardiology, Peking University First Hospital, No. 8 Xishiku St, Xicheng District, Beijing, 100034, China.
Eur J Clin Pharmacol. 2021 Mar;77(3):349-357. doi: 10.1007/s00228-020-03019-3. Epub 2020 Oct 13.
Statin-induced myopathy (SIM) is the commonest reason for discontinuation of statin therapy. The aim of this present meta-analysis is to assess the relationship between glycine amidinotransferase gene (GATM) polymorphism and risk of SIM.
MEDLINE, EMBASE, Web of Science, and Cochrane Library databases were searched systematically for case-control studies investigating the relationship between GATM polymorphism and SIM. Retrieved articles were carefully reviewed and assessed according to the inclusion criteria. Associations were assessed in pooled data by calculating odds ratio with 95% confidence intervals. Subgroup analysis was performed according to comedications and severity of SIM.
Six studies with 707 cases and 2321 controls were included in this meta-analysis. GATM rs9806699 G>A was associated with decreased risk of SIM (OR = 0.80, 95% CI 0.68-0.94, P = 0.006). This association remained significant in the subgroup with fibrates or niacin excluded. However, the association of rs9806699 G>A with severe SIM was not significant. In addition, another two variations at GATM, rs1719247 C>T, and rs1346268 T>C were also associated with declined risk of SIM.
GATM polymorphism including rs9806699 G>A, rs1719247 C>T, and rs1346268 T>C may be protective factors of SIM. GATM rs9806699 G>A may only exert protective effect on mild SIM cases. Our meta-analysis indicates that GATM polymorphism may represent a pharmacogenomics biomarker for predicting incidence of SIM, which contributes to risk stratification and optimizing statin adherence.
他汀类药物引起的肌病（SIM）是他汀类药物治疗中断的最常见原因。本荟萃分析旨在评估甘氨酰胺核苷酸转移酶基因（GATM）多态性与 SIM 风险之间的关系。
系统检索 MEDLINE、EMBASE、Web of Science 和 Cochrane 图书馆数据库，以评估研究 GATM 多态性与 SIM 之间关系的病例对照研究。仔细审查并根据纳入标准评估检索到的文章。通过计算合并数据的比值比（OR）及其 95%置信区间（CI）来评估相关性。根据合并用药和 SIM 严重程度进行亚组分析。
本荟萃分析纳入了 6 项研究，共 707 例病例和 2321 例对照。GATM rs9806699 G>A 与 SIM 风险降低相关（OR=0.80，95%CI 0.68-0.94，P=0.006）。在排除了贝特类药物或烟酸的亚组中，这种关联仍然显著。然而，rs9806699 G>A 与严重 SIM 的关联并不显著。此外，GATM 中的另外两个变异 rs1719247 C>T 和 rs1346268 T>C 也与 SIM 风险降低相关。
GATM 多态性（包括 rs9806699 G>A、rs1719247 C>T 和 rs1346268 T>C）可能是 SIM 的保护因素。GATM rs9806699 G>A 可能仅对轻度 SIM 病例具有保护作用。本荟萃分析表明，GATM 多态性可能是预测 SIM 发生率的一种药物基因组学生物标志物，有助于风险分层和优化他汀类药物的依从性。
