SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia

Santos, Paulo Caleb Júnior Lima; Gagliardi, Ana Carolina Moron; Miname, Márcio H.; Chacra, Ana Paula Marte; Santos, Raúl D.; Krieger, José Eduardo; Pereira, Alexandre C.

doi:10.1007/s00228-011-1125-1

Cited by 64 publications

(58 citation statements)

References 24 publications

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“…Results of the STRENGTH study showed a nonsignificant increase in myotoxicity in SLCO1B1*5 carriers taking atorvastatin [10]. In addition, three small studies and a meta-analysis did not find a statistically significant association between the SLCO1B1 521C variant and myotoxicity in patients using atorvastatin [13,16,61,62]. It must be taken into account that these studies included a rather small number of patients and there is a possibility that they were not able to detect an actual association.…”

Section: Probability Of Adr (%)mentioning

confidence: 82%

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ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case–control study

et al. 2015

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Section: Probability Of Adr (%)mentioning

confidence: 82%

“…All patients were of Croatian ancestry. Median (interquartile range) age was 56 (48-66) and 60 (53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70) in the groups of patients with and without ADRs, respectively. The gender distribution was identical, and atorvastatin median prescribed dose was the same in both groups.…”

Section: Subjectsmentioning

confidence: 99%

ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case–control study

et al. 2015

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“…In recent years, an increasing number of studies began to explore the role of SLCO1B1 polymorphisms in statin-induced ADRs. However, the results remain inconsistent and with limited power (Link et al 2008; de Keyser et al 2014; Marciante et al 2011; Voora et al 2009; Danik et al 2013; Donnelly et al 2011; Carr et al 2013; Santos et al 2012; Brunham et al 2012). …”

Section: Introductionmentioning

confidence: 99%

Association between SLCO1B1 −521T>C and −388A>G polymorphisms and risk of statin-induced adverse drug reactions: A meta-analysis

et al. 2016

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An increasing number of studies have investigated the association between SLCO1B1 −521T>C and −388A>G polymorphisms and the risk of statin-induced adverse drug reactions (ADRs), but the results have been inconsistent. This meta-analysis was performed to gain more insight into the relationship. PubMed, Embase, Cochrane Library and Web of Science were searched for relevant articles published before March 5th, 2015. The quality of included studies was evaluated by the Newcastle-Ottawa Quality scale. Pooled effect estimates (odds ratios [ORs] or hazard ratios [HRs) and corresponding 95 % confidence intervals (CIs) were calculated to assess the association in overall and subgroup analyses for various genetic models. Begg’s rank correlation test and Egger’s linear regression test were used to examine the publication bias. A total of nine cohort and four case–control studies involving 11, 246 statin users, of whom 2, 355 developing ADRs were included in the analysis. Combined analysis revealed a significant association between the SLCO1B1−521T>C polymorphism and increased risk for ADRs caused by various statins, but the synthesis heterogeneity was generally large (dominant model: pooled effect estimate = 1.85, 95 % CI 1.20–2.85, P = 0.005; I2 = 80.70 %, Pheterogeneity < 0.001). Subgroup analysis by statin type showed that the ADRs risk was significantly elevated among simvastatin users (dominant model: pooled effect estimate = 3.43, 95 % CI 1.80–6.52, P = 0.001; I2 = 59.60 %, Pheterogeneity = 0.060), but not among atorvastatin users. No significant relationship was found between the −388A>G polymorphism and ADRs caused by various statins (dominant model: pooled effect estimate = 0.94, 95 % CI 0.79–1.13, P = 0.526; I2 = 40.10 %, Pheterogeneity = 0.196). The meta-analysis suggests that SLCO1B1 −521T>C polymorphism may be a risk factor for statin-induced ADRs, especially in simvastatin therapy. Conversely, there may be no significant association for −388A>G polymorphism.

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“…Genotypes for the ACTN3 rs1815739 (R577X) polymorphism were detected by polymerase chain reaction (PCR) followed by high resolution melting (HRM) analysis with the Rotor Gene 6000® instrument (Qiagen, Courtaboeuf, France) [6]. Amplification of the fragments was performed using the primer sense 5'-TCAGTTCAAGGCAACACTGC-3' and antisense 5'-CTTCTGGATCTCACCCTGGA-3'.…”

Section: Methodsmentioning

confidence: 99%

ACTN3R577X polymorphism and long-term survival in patients with chronic heart failure

Bernardez‐Pereira

Santos

Mansur

et al. 2014

BMC Cardiovasc Disord

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BackgroundPrevious studies have shown the occurrence of actinin-3 deficiency in the presence of the R577X polymorphism in the ACTN3 gene. Our hypothesis is that this deficiency, by interfering with the function of skeletal muscle fiber, can result in a worse prognosis in patients with chronic heart failure.MethodsA prospective cohort study was conducted from 2002 to 2004. The eligibility criteria included diagnosis of chronic heart failure stage C from different etiologies. We excluded all patients with concomitant disease that could be related to poor prognosis. ACTN3 rs1815739 (R577X) polymorphism was detected by high resolution melting analysis. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between the baseline variables and the composite end-point of all-cause death was assessed using a Cox proportional hazards survival model.ResultsA total of 463 patients were included in this study. The frequency of the ACTN3 577X variant allele was 39.0%. The LVEF mean was 45.6 ± 18.7% and the most common etiology of this study was hypertensive. After a follow-up of five years, 239 (51.6%) patients met the pre-defined endpoint. Survival curves showed higher mortality in patients carrying RX or XX genotypes compared with patients carrying RR genotype (p = 0.01).ConclusionR577X polymorphism in the ACTN3 gene was independently associated with worse survival in patients with chronic heart failure. Further studies are necessary to ensure its use as a marker of prognosis for this syndrome.

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SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia

Abstract: Our findings reaffirm that the SLCO1B1 genetic risk appears to be greater in those patients receiving simvastatin compared with those receiving atorvastatin. This suggests that the importance of SLCO1B1 haplotypes depends on the specific statin that has been used.

Cited by 64 publications

References 24 publications

ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case–control study

ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case–control study

Association between SLCO1B1 −521T>C and −388A>G polymorphisms and risk of statin-induced adverse drug reactions: A meta-analysis

ACTN3R577X polymorphism and long-term survival in patients with chronic heart failure

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