Master's Dissertation
DOI
https://doi.org/10.11606/D.9.2008.tde-10062009-152818
Document
Author
Full name
Claudia Villazon Gonzales
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Hirata, Rosario Dominguez Crespo (President)
Bernik, Marcia Martins Silveira
Bertolami, Marcelo Chiara
Bernik, Marcia Martins Silveira
Bertolami, Marcelo Chiara
Title in Portuguese
Influência de variantes do receptor de LDL e da HMGCoA redutase na resposta à atorvastatina
Keywords in Portuguese
Atorvastatina
Farmacogenética
Hipercolesterolemia
HMGCoA redutase
Perfil lipidico
Polimorfismo
Receptores de LDL
Farmacogenética
Hipercolesterolemia
HMGCoA redutase
Perfil lipidico
Polimorfismo
Receptores de LDL
Abstract in Portuguese
A influencia dos polimorfismos genéticos de HMGCoA redutase (HMGCR) e LDL receptor (LDLR) na resposta a atorvastatina (10 mg/dia/4semanas) foi avaliada em individuos hipercolesterolemicos (HC). Amostras de sangue foram coletadas de 153 HC e 182 normolipidemicos (NL) para determinações de lipideos séricos e extração de DNA. Polimorfismos de troca única (SNP) HMGCR (A11898T e T24558G) e LDLR (C16730T, C20001T, G26857A) foram detectados. por PCR-RFLP. Os alelos HMGCR 11898T e 24558G foram associados com menores triglicérides e VLDL-C séricos nos grupos NL e HC (p<0,05). Além disso, o SNP HM0CR T24558G foi relacionado com HDL-C e apoAI séricos aumentados em resposta a atorvastatina no grupo HC. O alelo LDLR 20001 C foi associado com maior apoAI sérica basal no grupo NL (p=O,034) e com melhor resposta de apoAI a atorvastatina no grupo HC (p=O,045). Foi observada relação entre o haplótipo heterozigoto LDLR 20001 C/16730T e redução significativa de apoB e aumento de apoAI no soro após o tratamento com atorvastatina (pHMGCR A 11898T e T24558G influenciam os triglicérides e VLDL-C séricos independentemente do estado lipêmico e o haplótipo LDLR 20001 C/16730T está associado com melhor resposta de apoB e ApoAI séricos em resposta a atorvastatina.
Title in English
Influece of the LDL receptor and HMGCOA reductase variants in response to atorvastatin
Keywords in English
Atorvastatin
HMGCoA redudtase
Hypercholesterolemic
LDL receptors
Lipid profile
Pharmacogenetics
Polymorphisms
HMGCoA redudtase
Hypercholesterolemic
LDL receptors
Lipid profile
Pharmacogenetics
Polymorphisms
Abstract in English
Influence of the HMGCoA reductase (HMGCR) and LDL receptor (LDLR) gene polymorphisms on response to atorvastatin (10 mg/day/4weeks) was evaluated in hypercholesterolemic (HC) individuais. Blood samples were collected from 153 HC and 182 normolipidemic (NL) individuais for serum lipids determinations and DNA extratcion. Single nucleotide polymorphisms (SNP) HMGCR (A11898T e T24558G) and LDLR (C16730T, C20001T, G26857A) were detected by PCR-RFLP. HMGCR 11898T and 24558G alleles were associated with lower serum triglycerides and VLDL-C in NL and HC groups (p<0.05). Moreover, the SNP HMGCR T24558G was related to increased serum HDL-C and apoAI in response to atorvastatin in the HC group. The LDLR 20001 C allele was associated with higher basal serum apoAI in the NL group (p=0.034) and with better response of apoAI to atorvastatin in HC group (p=0.045). There was a relationship between heterozygote LDLR 20001 C/16730T haplotype and a significant reduction of apoB and increase in apoAI serum leveis after atorvastatin treatment (p<0.05). In conclusion, the HMGCR A11898T e T24558G SNPs influence serum triglycerides and VLDL-C independently of the lipemic status and LDLR 20001 C/16730T haplotype is associated with better serum apoB and Apol response to atorvastatin treatment.
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Publishing Date
2013-09-04
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