GATM Polymorphism Associated with the Risk for Statin-Induced Myopathy Does Not Replicate in Case-Control Analysis of 715 Dyslipidemic Individuals

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...

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Veröffentlicht in:Cell metabolism 2015-04, Vol.21 (4), p.622-627
Hauptverfasser: Luzum, Jasmine A., Kitzmiller, Joseph P., Isackson, Paul J., Ma, Changxing, Medina, Marisa W., Dauki, Anees M., Mikulik, Eduard B., Ochs-Balcom, Heather M., Vladutiu, Georgirene D.
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container_end_page 627
container_issue 4
container_start_page 622
container_title Cell metabolism
container_volume 21
creator Luzum, Jasmine A.
Kitzmiller, Joseph P.
Isackson, Paul J.
Ma, Changxing
Medina, Marisa W.
Dauki, Anees M.
Mikulik, Eduard B.
Ochs-Balcom, Heather M.
Vladutiu, Georgirene D.
description 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. [Display omitted] •The association of GATM rs9806699 with statin-induced myopathy was not replicated•GATM rs9806699 allele/genotype frequencies were similar in SIM cases and controls•Meta-analysis yielded a marginal, but null, association of GATM rs9806699 with SIM Statin-induced myopathy (SIM) is the most common reason for discontinuation of statin therapy. While a polymorphism affecting the gene encoding glycine amidinotransferase (GATM rs9806699) was previously associated with reduced SIM, Luzum et al. do not replicate this association in a large, multicenter SIM case-control study including 715 individuals.
doi_str_mv 10.1016/j.cmet.2015.03.003
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A polymorphism affecting the gene encoding glycine amidinotransferase (GATM rs9806699 G &gt; 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. [Display omitted] •The association of GATM rs9806699 with statin-induced myopathy was not replicated•GATM rs9806699 allele/genotype frequencies were similar in SIM cases and controls•Meta-analysis yielded a marginal, but null, association of GATM rs9806699 with SIM Statin-induced myopathy (SIM) is the most common reason for discontinuation of statin therapy. 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A polymorphism affecting the gene encoding glycine amidinotransferase (GATM rs9806699 G &gt; 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. 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subjects Amidinotransferases - genetics
Gene Frequency
Genetic Association Studies
Genotype
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects
Logistic Models
Muscular Diseases - chemically induced
Muscular Diseases - genetics
Odds Ratio
Polymorphism, Single Nucleotide - genetics
title 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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