title: Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia.
abstract: Familial hypercholesterolaemia (FH) is an autosomal dominant disease characterized by elevated levels of low-density lipoprotein-cholesterol (LDL-C). Phenotypic expression is highly variable, being influenced by diet, age, gender, body mass index, apolipoprotein E genotype and type of LDL-receptor gene mutation. Microsomal triglyceride (TG) transfer protein (MTP) is a protein involved in lipid metabolism. Polymorphism MTP -493 GT has been shown to modulate lipid levels in several populations. To analyse the effect of this polymorphism in the lipid phenotype expression of FH and treatment response, we studied a sample of 222 Spanish FH patients, of whom 147 were studied before and after treatment with 20 mg of atorvastatin daily during 6 weeks. The variant was analysed by polymerase chain reaction amplification and single-strand confirmation polymorphism. Treatment reduced LDL-C, total cholesterol and TGs. Baseline fasting TGs and very-low-density lipoprotein cholesterol levels were lower in female T allele carriers (TG: 111+/-51 mg/dl GG, 89+/-35 mg/dl GT, 83+/-26 mg/dl TT, P=0.022; very-low-density lipoprotein cholesterol: 24+/-13 mg/dl GG, 16+/-5 mg/dl GT, 17+/-5 mg/dl TT, P=0.018). Triglyceride response to atorvastatin was modulated by this polymorphism in men (P=0.009), but not in women, although differences between genotypes were maintained after treatment. In conclusion, the MTP -493 GT polymorphism modulates pre- and post-treatment plasma TG values of FH in Spanish subjects in a gender-specific way. Other environmental and genetic factors likely also modulate this response.
authors.affiliation: Unidad Mixta de Investigación, Hospital Clínico Universitario de Valencia, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: García-García
authors.forename: Cintia
authors.initials: C
authors.lastname: González
authors.forename: José T
authors.initials: JT
authors.lastname: Real
authors.forename: José J
authors.initials: JJ
authors.lastname: Martín de Llano
authors.forename: Verónica
authors.initials: V
authors.lastname: González-Albert
authors.forename: Miguel
authors.initials: M
authors.lastname: Civera
authors.forename: Felipe J
authors.initials: FJ
authors.lastname: Chaves
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ascaso
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
mesh_terms: D000483:Alleles; D001057:Apolipoproteins E / Q000378:metabolism; D000069059:Atorvastatin; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005215:Fasting; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006538:Heptanoic Acids / Q000494:pharmacology*; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000378:metabolism; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry; D008297:Male; D009154:Mutation; D010597:Pharmacogenetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011758:Pyrroles / Q000494:pharmacology*; D012737:Sex Factors; D014280:Triglycerides / Q000235:genetics* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D002352:Carrier Proteins; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011758:Pyrroles; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D004247:DNA; D002784:Cholesterol; D000069059:Atorvastatin