title: A functional SNP upstream of the beta-2 adrenergic receptor gene (ADRB2) is associated with obesity in Oceanic populations.
abstract: OBJECTIVE
  Obesity is a growing health concern in the Oceanic populations. To investigate the genetic factors associated with adult obesity in the Oceanic populations, the association of single nucleotide polymorphisms (SNPs) of the beta-2 adrenergic receptor (ADRB2) gene with obesity was examined in 694 adults living in Tonga and Solomon Islands.
  
  
  RESULTS
  A screening for variation in 16 Oceanic subjects detected 17 SNPs in the entire region of ADRB2, of which nine SNPs including two non-synonymous ones, rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu), were further genotyped for all subjects. The rs34623097-A allele, at a SNP located upstream of ADRB2, showed the strongest association with risk for obesity in a logistic regression analysis adjusted for age, sex, and population (P=5.6 × 10(-4), odds ratio [OR]=2.5, 95% confidence interval [CI]=1.5-4.2). The 27Glu was also significantly associated with obesity in the single-point association analysis (P=0.013, OR=2.0, 95%CI=1.2-3.4); however, this association was no longer significant after adjustment for rs34623097 since these SNPs were in linkage disequilibrium with each other. A copy of the obesity-risk allele, rs34623097-A, led to a 1.6 kg/m(2) increase in body mass index (BMI; defined as weight in kilograms divided by height in meters squared) (P=0.0019). A luciferase reporter assay indicated that rs34623097-A reduced the transcriptional activity of the luciferase reporter gene by approximately 10% compared with rs34623097-G. An electrophoretic mobility shift assay demonstrated that rs34623097 modulated the binding affinity with nuclear factors. An evolutionary analysis implies that a G>A mutation at rs34623097 occurred in the Neandertal genome and then the rs34623097-A allele flowed into the ancestors of present-day humans.
  
  
  CONCLUSIONS
  The present results suggest that rs34623097-A, which would lead to lower expression of ADRB2, contributes to the onset of obesity in the Oceanic populations.
authors.affiliation: Department of Molecular and Genetic Epidemiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Naka
authors.forename: K
authors.initials: K
authors.lastname: Hikami
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: M
authors.initials: M
authors.lastname: Koga
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.forename: R
authors.initials: R
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Furusawa
authors.forename: K
authors.initials: K
authors.lastname: Natsuhara
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: M
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ataka
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: T
authors.initials: T
authors.lastname: Inaoka
authors.forename: S
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumura
authors.forename: R
authors.initials: R
authors.lastname: Ohtsuka
authors.forename: N
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: J
authors.initials: J
authors.lastname: Ohashi
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001823:Body Composition; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008542:Melanesia / Q000453:epidemiology; D008875:Middle Aged; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011506:Proteins / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D014058:Tonga / Q000453:epidemiology
chemical_list: D011506:Proteins; D018343:Receptors, Adrenergic, beta-2; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human