2024-03-28T20:56:27Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02011130
2023-08-03T05:35:08Z
1642838163960:1642838338003
1642838403551:1642838407795
A functional SNP upstream of the beta-2 adrenergic receptor gene (ADRB2) is associated with obesity in Oceanic populations
Naka, I
Hikami, K
Nakayama, K
Koga, M
Nishida, N
Kimura, R
Furusawa, T
Natsuhara, K
Yamauchi, T
Nakazawa, M
Ataka, Y
Ishida, T
Inaoka, T
Iwamoto, S
Matsumura, Y
Ohtsuka, R
Tsuchiya, N
Ohashi, J
open access
Creative Commons Attribution-NonCommercial-NoDerivs 3.0
https://creativecommons.org/licenses/by-nc-nd/3.0/
beta-2 adrenergic receptor gene (ADRB2)
body mass index (BMI)
obesity
Oceanic population
polymorphism
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.\nRESULTS: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.\nCONCLUSION: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.
論文
Springer Nature
2012-12-11
eng
journal article
VoR
http://hdl.handle.net/20.500.12000/46966
http://hdl.handle.net/20.500.12000/46966
https://u-ryukyu.repo.nii.ac.jp/records/2011130
https://doi.org/10.1038/ijo.2012.206
https://doi.org/10.1038/ijo.2012.206
0307-0565
1476-5497
International Journal of Obesity
37
9
1204
1210
https://u-ryukyu.repo.nii.ac.jp/record/2011130/files/ijo2012206.pdf