The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia
| العنوان: | The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia |
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| المؤلفون: | Alexandre C. Pereira, Aline Cruz Morgan, José Eduardo Krieger, Cinthia E. Jannes, Raul D. Santos, Paulo Caleb Junior Lima Santos |
| المصدر: | Pharmacogenetics and Genomics |
| بيانات النشر: | Lippincott Williams & Wilkins, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Ubiquitin-Protein Ligases, Familial hypercholesterolemia, MYLIP, Disease, Bioinformatics, Hyperlipoproteinemia Type II, chemistry.chemical_compound, Internal medicine, Genetic variation, Genetics, medicine, Atorvastatin, Humans, Pyrroles, General Pharmacology, Toxicology and Pharmaceutics, Molecular Biology, Gene, Genetics (clinical), Aged, DNA Primers, Polymorphism, Genetic, familial hypercholesterolemia, lipid-lowering therapy, Base Sequence, Cholesterol, business.industry, Anticholesteremic Agents, Original Articles, Middle Aged, medicine.disease, 3. Good health, Endocrinology, chemistry, Heptanoic Acids, IDOL, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, pharmacogenetic, Molecular Medicine, lipids (amino acids, peptides, and proteins), Female, business, Dyslipidemia, Brazil |
| الوصف: | Supplemental Digital Content is available in the text. Background A previous study reported that the myosin regulatory light chain interacting protein (MYLIP) might serve as a novel therapeutic class for treating dyslipidemia. It contributes to variations in the levels of circulating low-density lipoprotein cholesterol (LDL-C), promoting the degradation of LDL–LDLR, thus limiting absorption. The effect of genetic variation in the MYLIP gene in a disease scenario characterized by mutations in the LDLR gene has not been previously evaluated. Objective The aim of this study was to assess the effect of the p.N342S variant on the response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia (FH). Patients and methods A total of 156 patients with heterozygous FH were followed up for 12 months and received lipid-lowering therapy (different doses of atorvastatin with the addition of ezetimibe in over half the patients of each genotype group). Cholesterol data were assessed, and analysis of the MYLIP rs9370867 (p.N342S) genotypes was carried out by melting curve analysis. Results Baseline total cholesterol and baseline LDL-C levels were not different between genotypes. After 1 year of treatment, LDL-C responses (expressed as mg/dl and as %) were significantly different among genotypes (AA: −79±68 and −39±27, GA: −60±79 and −27±32, and GG: −30±83 and −15±38; P=0.02 and 0.005, respectively). In addition, FH patients carrying the AA genotype were more likely to achieve LDL-C levels of less than 130 mg/dl after 1 year of treatment (75.0%) compared with patients with the GG and GA genotypes (34.5 and 34.8%, respectively; P=0.001). Conclusion Our study indicates that MYLIP p.N342S might be a pharmacogenetic marker for lipid-lowering therapy in patients with FH. |
| اللغة: | English |
| تدمد: | 1744-6880 1744-6872 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21665b1e3e85f0c1cab81d617edc9a45Test http://europepmc.org/articles/PMC4206345Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....21665b1e3e85f0c1cab81d617edc9a45 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17446880 17446872 |
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