title: The presence of at least three alleles of the ADRB3 Trp64Arg (C/T) and UCP1 -3826A/G polymorphisms is associated with protection to overweight/obesity and with higher high-density lipoprotein cholesterol levels in Caucasian-Brazilian patients with type 2 diabetes.
abstract: BACKGROUND
  We investigated whether the -3826A/G polymorphism (rs1800592) of the uncoupling protein 1 gene (UCP1) and the Trp64Arg polymorphism (rs4994) of the β3-adrenergic receptor gene (ADRB3) are associated with type 2 diabetes mellitus (T2DM) and features of metabolic syndrome in a Brazilian-Caucasian population.
  
  
  METHODS
  Both polymorphisms were genotyped in 1015 T2DM patients and 561 nondiabetic subjects. The combined effect of both polymorphisms on T2DM and metabolic syndrome-related parameters was analyzed according to a triallelic inheritance pattern, by which at least three minor alleles from two loci are necessary for trait manifestation.
  
  
  RESULTS
  UCP1 -3826A/G and ADRB3 Trp64Arg polymorphisms were not associated with T2DM (P>0.05). Patients carrying the ADRB3 64Arg allele had higher fasting plasma glucose and high-density lipoprotein cholesterol (HDL-C) than patients with the Trp64Trp genotype (P=0.0001 and P=0.015, respectively). The 64Arg allele was also associated with protection against overweight/obesity (body mass index ≥ 25 kg/m(2); odds ratio [OR]=0.598; P=0.014). Interestingly, prevalence of overweight/obesity was lower among carriers of at least three minor alleles of the -3826A/G and ADRB3 Trp64Arg polymorphisms than among patients with fewer than three minor alleles (54.5% vs. 79.1%; OR=0.288; P=0.007, respectively). Subjects with at least three minor alleles also had higher HDL-C levels (P=0.018).
  
  
  CONCLUSIONS
  UCP1 -3826A/G and ADRB3 Trp64Arg polymorphisms may have a combined effect in the modulation of overweight/obesity and HDL-C levels in type 2 diabetes mellitus (T2DM) Caucasian-Brazilian patients.
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre , Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brasil .
authors.forename: Letícia A
authors.initials: LA
authors.lastname: Brondani
authors.forename: Guilherme C K
authors.initials: GC
authors.lastname: Duarte
authors.forename: Luís H
authors.initials: LH
authors.lastname: Canani
authors.forename: Daisy
authors.initials: D
authors.lastname: Crispim
mesh_terms: D000368:Aged; D000483:Alleles; D001786:Blood Glucose; D001938:Brazil; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000208:ethnology / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D016017:Odds Ratio; D050177:Overweight / Q000235:genetics*; D011110:Polymorphism, Genetic; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D012307:Risk Factors; D011795:Surveys and Questionnaires; D000071256:Uncoupling Protein 1; D044465:White People
chemical_list: C568534:ADRB3 protein, human; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007473:Ion Channels; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1