Dataset Information

GATM polymorphism associated with the risk for statin-induced myopathy does not replicate in case-control analysis of 715 dyslipidemic individuals.

ABSTRACT: Statin-induced myopathy (SIM) is the most common reason for discontinuation of statin therapy. A polymorphism affecting the gene encoding glycine amidinotransferase (GATM rs9806699 G > A) was previously associated with reduced risk for SIM. Our objective was to replicate the GATM association in a large, multicenter SIM case-control study. Mild and severe SIM cases and age- and gender-matched controls were enrolled. Participants were genotyped, and associations were tested (n = 715) using chi-square and logistic regression with consideration for SIM severity and exclusion of subjects with potentially confounding comedications. The minor allele (A) frequencies of GATM rs9806699 in the controls (n = 106), mild SIM (n = 324), and severe SIM (n = 285) cases were 0.26, 0.28, and 0.29, respectively (p = 0.447). The unadjusted odds ratio for the A allele for any SIM (mild or severe) was 1.14 (0.82-1.61; p = 0.437), which remained nonsignificant in all models. Our results do not replicate the association between GATM rs9806699 and SIM.

SUBMITTER: Luzum JA

PROVIDER: S-EPMC4394188 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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GATM polymorphism associated with the risk for statin-induced myopathy does not replicate in case-control analysis of 715 dyslipidemic individuals.

Luzum Jasmine A JA Kitzmiller Joseph P JP Isackson Paul J PJ Ma Changxing C Medina Marisa W MW Dauki Anees M AM Mikulik Eduard B EB Ochs-Balcom Heather M HM Vladutiu Georgirene D GD

Cell metabolism 20150401 4

Statin-induced myopathy (SIM) is the most common reason for discontinuation of statin therapy. A polymorphism affecting the gene encoding glycine amidinotransferase (GATM rs9806699 G > A) was previously associated with reduced risk for SIM. Our objective was to replicate the GATM association in a large, multicenter SIM case-control study. Mild and severe SIM cases and age- and gender-matched controls were enrolled. Participants were genotyped, and associations were tested (n = 715) using chi-squ ...[more]

PMID: 25863251

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Project description:Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association. Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle-Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27-3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43-3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41-10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47-5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64-5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38-6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74-2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57-3.12, P = 0.52). The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.

Dataset Information

GATM polymorphism associated with the risk for statin-induced myopathy does not replicate in case-control analysis of 715 dyslipidemic individuals.

Publications

GATM polymorphism associated with the risk for statin-induced myopathy does not replicate in case-control analysis of 715 dyslipidemic individuals.

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