title: The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes.
  
  
  METHODS
  This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%-10%) managed with metformin and a lifestyle program. Each person with the risk allele (R230C) was matched by age, gender and BMI to three others with the wild type variant (R230R). Following a four week stabilization period, only participants with a greater than 70% adherence to metformin and a stable body weight were prescribed glyburide therapy for a further 16 weeks. The main outcome variable was the glyburide dose required to achieve treatment goals.
  
  
  RESULTS
  No significant difference was observed in the glucose lowering effect of glyburide between subjects with the R230C and R230R alleles. However, the dose of sulfonylurea was significantly higher in the R230C participants compared with the R230R subjects (3.3±2.1 vs 6.3±5 mg/day, p<0.001). A higher percentage of R230C participants required at least 5mg of glyburide per day to achieve treatment goals. The glyburide dose was determined by the presence of the risk allele, among other factors.
  
  
  CONCLUSIONS
  Patients with type 2 diabetes who have the R230C allele of ABCA1 needed a higher dose of glyburide in order to achieve the same glucose lowering effect as that in persons with the wild type variant.
authors.affiliation: Department of Endocrinology and Metabolism. Instituto Nacional de Ciencias Médicas y Nutrición. México City, México. caguilarsalinas@yahoo.com
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: Linda Liliana
authors.initials: LL
authors.lastname: Muñoz-Hernandez
authors.forename: Monica
authors.initials: M
authors.lastname: Cobos-Bonilla
authors.forename: Marcos Rafael
authors.initials: MR
authors.lastname: Ramírez-Márquez
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Ordoñez-Sanchez
authors.forename: Roopa
authors.initials: R
authors.lastname: Mehta
authors.forename: Roberto
authors.initials: R
authors.lastname: Medina-Santillan
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Tusie-Luna
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D001120:Arginine; D003545:Cysteine; D005905:Glyburide