title: Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians.
abstract: OBJECTIVE
  To investigate whether (a) variants within the dopamine D2 receptor gene (DRD2) are associated with obesity and type 2 diabetes in Pima Indians, and (b) whether variation in this gene could be responsible for previously observed linkage to these phenotypes, at chromosome location 11q23-24, in this population.
  
  
  METHODS
  Two single nucleotide polymorphisms (SNPs), Ser311Cys and TaqIA, within the DRD2 gene were genotyped by allelic discrimination PCR in subjects who had provided evidence of linkage to diabetes and obesity in an autosome-wide scan.
  
  
  METHODS
  A total of 1,187 subjects were genotyped, including 947 full heritage Pima Indians (80%). Descriptive statistics for all subjects analyzed, for whom clinical data were available, were (mean+/-s.d.): age at time of last exam = 41 +/- 15 y; birth year=1950 +/- 14; age-sex-adjusted body mass index (BMI; adjusted to a mean age of 35y)=36 +/- 8kg/m2; male = 44%; diabetic = 57%. For full heritage Pimas only: age = 43 +/- 15 y; birth year = 1948 +/- 14; sex- age-adjusted BMI = 36 +/- 8 kg/m2; male = 43%; diabetic = 59%.
  
  
  RESULTS
  Neither polymorphism was significantly associated with diabetes in full heritage Pimas. Individuals with a 'CG' genotype at the Ser311Cys SNP had a higher BMI than those with a 'CC' genotype (36.7 vs 35.5 kg/m2, P= 0.04). Linkage analysis of BMI, adjusted for either polymorphism, resulted in LOD scores that were similar to those obtained without adjustment.
  
  
  CONCLUSIONS
  Heterozygotes at the Ser311Cys DRD2 polymorphism had a slightly higher BMI than homozygotes, however neither the Ser311Cys nor the TaqIA polymorphism accounted for the linkage with BMI on chromosome 11 in Pima Indians.
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Digestive Diabetes and Kidney Diseases, National Institutes of Health, Arizona, USA. JenkinsonC@UTHSCSA.EDU
authors.forename: C P
authors.initials: CP
authors.lastname: Jenkinson
authors.forename: R
authors.initials: R
authors.lastname: Hanson
authors.forename: K
authors.initials: K
authors.lastname: Cray
authors.forename: C
authors.initials: C
authors.lastname: Wiedrich
authors.forename: W C
authors.initials: WC
authors.lastname: Knowler
authors.forename: C
authors.initials: C
authors.lastname: Bogardus
authors.forename: L
authors.initials: L
authors.lastname: Baier
mesh_terms: D000328:Adult; D001130:Arizona; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: D017448:Receptors, Dopamine D2