Influence of SREBP-2 and SCAP Gene Polymorphisms on Lipid-Lowering Response to Atorvastatin in a Cohort of Chilean Subjects with Amerindian Background

Lagos, Jenny; Zambrano, Tomás; Rosales, Alexy; Salazar, Luis A.

doi:10.1007/s40291-014-0094-3

Cited by 12 publications

(10 citation statements)

References 47 publications

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“…Attenuated LDL‐level lowering in response to atorvastatin therapy was demonstrated in patients with another HMGCR polymorphism, rs12916 T allele, indicating an importance of this gene in relation to the statin response . Another study in Chilean patients showed ‐ SREBF2 G1784C polymorphism was associated with attenuated response to atorvastatin (GG had 9% smaller Tc‐level reduction vs GC and 8% smaller reduction vs CC, p=0.015; GG had 15% smaller LDL‐level reduction vs GC and 12% smaller reduction vs CC, p=0.013) …”

Section: Atorvastatinmentioning

confidence: 98%

Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia

et al. 2017

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Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect. Many studies have explored the variation in statins' pharmacokinetic and pharmacodynamic parameters; however, to our knowledge, few have established definitive relationships between the genetic polymorphisms and patient outcomes, such as cardiovascular events. In this review article, we provide a statin-based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future. Although currently available studies are often small or retrospective, and may have conflicting results, they may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed in the future when more patient outcomes-based studies are available. We also summarize the clinically relevant evidence currently available to assist clinicians with providing personalized pharmacotherapy for patients requiring statin therapy.

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Section: Atorvastatinmentioning

confidence: 98%

Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia

et al. 2017

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“…Another study found SCAP-796I isoform (A allele) is associated with higher LDL in Caucasian female[7]. A study in Chilean hypercholesterolemic individuals demonstrated that rs12487736 were not associated with pharmacogenomic response to atorvastatin[8], however, rs12487736 polymorphism G allele carriers had a significant better hypolipidemic response than AA carriers in an Indian study[30]. Further adjustment for blood lipid parameters barely influenced the significant associations between SCAP polymorphisms and BP, which showed that the associations between SCAP polymorphisms and BP are independent of blood lipid level.…”

Section: Discussionmentioning

confidence: 99%

“…The rs12487736 polymorphism is a common polymorphism located in exon 16. It is associated with obesity and might contribute to the serum levels of cholesterol in different populations[7,8]. The rs12490383 polymorphism was reported to be associated with body mass index (BMI) change[9].…”

Section: Introductionmentioning

confidence: 99%

Genetic variations in sterol regulatory element binding protein cleavage-activating protein (SCAP) are associated with blood pressure in overweight/obese Chinese children

et al. 2017

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ObjectivePrevious studies demonstrated a role of variations in sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) in obesity and blood lipids. But the associations between SCAP polymorphisms and blood pressure (BP) are not clear. This study aimed to investigate the relationship between genetic variations in SCAP and BP phenotypes in a Chinese pediatric population.MethodsA case-control study on 702 high blood pressure (HBP) children and 1319 controls was conducted to explore the correlation between single nucleotide polymorphism markers (rs12487736 and rs12490383) of SCAP and BP phenotypes. The associations with continuous and categorical variables were examined by linear regression and logistic regression models under a dominant genetic model for the minor rs12487736 A allele and rs12490383 T allele.ResultsThe rs12487736 polymorphism was significantly associated with systolic BP (SBP) (β = 1.66, P = 0.003) and diastolic BP (DBP) (β = 1.35, P = 0.024) with age, age-squared, sex, study population and body mass index (BMI) adjusted under the dominant genetic model. The rs12490383 polymorphism was significantly associated with SBP (β = 1.71, P = 0.004) and SHBP (OR = 1.39, 95%CI: 1.04–1.86, P = 0.027). When analyzed by BMI categories, in the normal-weight children, no significant association between the SCAP polymorphisms and BP phenotypes was observed (all P > 0.05). However, in the overweight/obese children, rs12487736 was significantly associated with SBP (β = 1.6, P = 0.019) and SHBP (OR = 1.36, 95%CI: 1.02–1.82; P = 0.037), rs12490383 was associated with SBP (β = 2.04, P = 0.004) and SHBP (OR = 1.50, 95%CI: 1.10–2.05; P = 0.01).ConclusionsThis study demonstrated that SCAP rs12487736 and rs12490383 were significantly associated with SBP and SHBP in overweight/obese Chinese children. It provided the evidence for association of SCAP with SBP.

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“…However, subjects evaluated in the PROSPER cohort were mostly elderly with a mean age of 75 years, while individuals enrolled in our study had a mean age more than 20 years younger, a covariate that can define lipid response [49]. Also, the MAFs found in the PROSPER trial were more related to a Caucasian phenotype, contrasting with the Amerindian background reported for Chilean subjects [50]. Ethnicity has been reported to be a decisive factor contributing to control of dyslipidemia [51].…”

Section: Discussionmentioning

confidence: 59%

Efficacy of Ezetimibe Is Not Related to NPC1L1 Gene Polymorphisms in a Pilot Study of Chilean Hypercholesterolemic Subjects

et al. 2015

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Influence of SREBP-2 and SCAP Gene Polymorphisms on Lipid-Lowering Response to Atorvastatin in a Cohort of Chilean Subjects with Amerindian Background

Abstract: The G1784C polymorphism of SREBP-2 gene affects atorvastatin response in Chilean subjects with Amerindian background, and may be an important marker for predicting efficacy of lipid-lowering therapy.

Cited by 12 publications

References 47 publications

Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia

Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia

Genetic variations in sterol regulatory element binding protein cleavage-activating protein (SCAP) are associated with blood pressure in overweight/obese Chinese children

Efficacy of Ezetimibe Is Not Related to NPC1L1 Gene Polymorphisms in a Pilot Study of Chilean Hypercholesterolemic Subjects

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