Polymorphisms in the multidrug resistance-1 (MDR1) gene influence the response to atorvastatin treatment in a gender-specific manner

Kajinami, Kouji; Brousseau, Margaret E.; Ordovas, José M.; Schaefer, Ernst J.

doi:10.1016/j.amjcard.2004.01.014

Cited by 115 publications

(73 citation statements)

References 17 publications

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“…In a sample of Brazilians of European descent (Munshi 2012), and a sample from USA (Mega et al 2009), no such associations were detected for these polymorphisms. In this study, The TT genotype of the C3435T, and TT genotype at MDR1 G2677T polymorphism were associated with lower levels of LDL after atorvastatin treatment among Jordanians, similar to results of Kajinami et al (2004). The variation in SNPs effect on response to atrovastatin is possibly due to different genetic backgrounds.…”

Section: Discussionsupporting

confidence: 80%

“…Kajinami et al 2004 reported a positive contribution for the TT genotype of the C3435T, but not the G2677T/A polymorphism, to the lipid lowering effect of atorvastatin among females from the USA (Kajinami et al 2004). In a sample of Brazilians of European descent (Munshi 2012), and a sample from USA (Mega et al 2009), no such associations were detected for these polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported changes in atorvastatin treatment outcomes in association with MDR-1 polymorphisms (Kajinami et al 2004;Munshi 2012). For example, in a study from USA, common variants of MDR1 gene such as the C3435T, were associated with a smaller reduction in LDL and with a larger increase in HDL levels, relative to variant allele carriers (Kajinami et al 2004). However, other studies among Brazilian of European descents and USA populations, found no significant relation between atorvastatin response and MDR1 C3435T polymorphism (Mega et al 2009;Rodrigues et al 2005).…”

Section: Introductionmentioning

confidence: 91%

“…The drug reduces levels of total cholesterol, lowdensity lipoprotein (LDL)-cholesterol, and triglyceride, and increases high-density lipoprotein (HDL)-cholesterol in patients with a wide variety of dyslipidemia (Lennernas 2003). Previous studies have reported changes in atorvastatin treatment outcomes in association with MDR-1 polymorphisms (Kajinami et al 2004;Munshi 2012). For example, in a study from USA, common variants of MDR1 gene such as the C3435T, were associated with a smaller reduction in LDL and with a larger increase in HDL levels, relative to variant allele carriers (Kajinami et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

et al. 2014

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The MDR1 gene encodes for P-glycoprotein (P-gp), which is an efflux transporter at the cell membrane. The P-gp has wide substrate specificity for multiple medications including the lipid lowering drug, atorvastatin. In this study, we investigated the possible association between three common MDR1 gene polymorphisms (G2677T, C3435T, and C1236T), and the lipid lowering effect of atorvastatin among Jordanians. Lipid and lipoproteins were measured in blood samples collected from patients (n = 201) at baseline and during atorvastatin treatment. MDR1 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Both the TT genotype of G2677T and the TT genotype of the C3435T polymorphisms were associated with lower levels of low-density lipoproteins after atorvastatin treatment. However, the effects of atorvastatin on the levels of total cholesterol, triglycerides, and high-density lipoprotein, were not correlated with any of the genotypes in both polymorphisms. Finally, the C1236T polymorphism was not associated with the lipid lowering effect of atorvastatin. In conclusion, the MDR1 gene polymorphisms G2677T, and C3435T, but not C1236T were associated with the lipid lowering effect of atorvastatin among Jordanians.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

et al. 2014

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“…One published association with rs1045642 in ABC B1 (MDR1) was found in a gender-specific manner. 9 We did not replicate All SNPs noted in Table 1 with a significant association with any outcome are listed with the appropriate phenotype and statin. In the last column, the direction of change in our study relative to the original study is noted.…”

Section: Resultsmentioning

confidence: 99%

An association study of 43 SNPs in 16 candidate genes with atorvastatin response

et al. 2005

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Variation in individual response to statin therapy has been widely studied for a potential genetic component. Multiple genes have been identified as potential modulators of statin response, but few study findings have replicated. To further examine these associations, 2735 individuals on statin therapy, half on atorvastatin and the other half divided among fluvastatin, lovastatin, pravastatin and simvastatin were genotyped for 43 SNPs in 16 genes that have been implicated in statin response. Associations with lowdensity lipoprotein cholesterol (LDL-C) lowering, total cholesterol lowering, HDL-C elevation and triglyceride lowering were examined. The only significant associations with LDL-C lowering were found with apoE2 in which carriers of the rare allele who took atorvastatin lowered their LDL-C by 3.5% more than those homozygous for the common allele and with rs2032582 (S893A in ABCB1) in which the two groups of homozygotes differed by 3% in LDL-C lowering. These genetic effects were smaller than those observed with the demographic variables of age and gender. The magnitude of all the differences found is sufficiently small that genetic data from these genes should not influence clinical decisions on statin administration.

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Claims of Sex Differences

Patsopoulos

Tatsioni²,

Ioannidis³

2007

JAMA

131

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Polymorphisms in the multidrug resistance-1 (MDR1) gene influence the response to atorvastatin treatment in a gender-specific manner

Cited by 115 publications

References 17 publications

The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians

An association study of 43 SNPs in 16 candidate genes with atorvastatin response

Claims of Sex Differences

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