A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis
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A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis. / Dahlman, Ingrid; Dicker, Andrea; Jiao, Hong; Kere, Juha; Blomqvist, Lennart; van Harmelen, Vanessa; Hoffstedt, Johan; Borch-Johnsen, Knut; Jorgensen, Torben; Hansen, Torben; Pedersen, Oluf; Laakso, Markku; Arner, Peter.
In: American Journal of Human Genetics, Vol. 80, No. 6, 2007, p. 1115-24.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis
AU - Dahlman, Ingrid
AU - Dicker, Andrea
AU - Jiao, Hong
AU - Kere, Juha
AU - Blomqvist, Lennart
AU - van Harmelen, Vanessa
AU - Hoffstedt, Johan
AU - Borch-Johnsen, Knut
AU - Jorgensen, Torben
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Laakso, Markku
AU - Arner, Peter
PY - 2007
Y1 - 2007
N2 - The G-protein-coupled receptor GPR74 is a novel candidate gene for body weight regulation. In humans, it is predominantly expressed in brain, heart, and adipose tissue. We report a haplotype in the GPR74 gene, ATAG, with allele frequency ~4% in Scandinavian cohorts, which was associated with protection against obesity in two samples selected for obese and lean phenotypes (odds ratio for obesity 0.48 and 0.62; nominal P=.0014 and .014; n=1,013 and 1,423, respectively). In a population-based sample, it was associated with lower waist (P=.02) among 3,937 men and with obesity protection (odds ratio 0.36; P=.036) among those selected for obese or lean phenotypes. The ATAG haplotype was associated with increased adipocyte lipid mobilization (lipolysis) in vivo and in vitro. In human fat cells, GPR74 receptor stimulation and inhibition caused a significant and marked decrease and increase, respectively, of lipolysis, which could be linked to catecholamine stimulation of adipocytes through beta -adrenergic receptors. These findings suggest that a common haplotype in the GPR74 gene protects against obesity, which, at least in part, is caused by a relief of inhibition of lipid mobilization from adipose tissue. The latter involves a cross-talk between GPR74 and beta -adrenoceptor signaling to lipolysis in fat cells.
AB - The G-protein-coupled receptor GPR74 is a novel candidate gene for body weight regulation. In humans, it is predominantly expressed in brain, heart, and adipose tissue. We report a haplotype in the GPR74 gene, ATAG, with allele frequency ~4% in Scandinavian cohorts, which was associated with protection against obesity in two samples selected for obese and lean phenotypes (odds ratio for obesity 0.48 and 0.62; nominal P=.0014 and .014; n=1,013 and 1,423, respectively). In a population-based sample, it was associated with lower waist (P=.02) among 3,937 men and with obesity protection (odds ratio 0.36; P=.036) among those selected for obese or lean phenotypes. The ATAG haplotype was associated with increased adipocyte lipid mobilization (lipolysis) in vivo and in vitro. In human fat cells, GPR74 receptor stimulation and inhibition caused a significant and marked decrease and increase, respectively, of lipolysis, which could be linked to catecholamine stimulation of adipocytes through beta -adrenergic receptors. These findings suggest that a common haplotype in the GPR74 gene protects against obesity, which, at least in part, is caused by a relief of inhibition of lipid mobilization from adipose tissue. The latter involves a cross-talk between GPR74 and beta -adrenoceptor signaling to lipolysis in fat cells.
KW - Adipocytes
KW - Adrenergic alpha-Agonists
KW - Adrenergic alpha-Antagonists
KW - Adult
KW - Alleles
KW - Bucladesine
KW - Cell Differentiation
KW - Cohort Studies
KW - Dose-Response Relationship, Drug
KW - Drug Interactions
KW - Female
KW - Gene Frequency
KW - Haplotypes
KW - Humans
KW - Linkage Disequilibrium
KW - Lipolysis
KW - Male
KW - Middle Aged
KW - Norepinephrine
KW - Odds Ratio
KW - Polymorphism, Single Nucleotide
KW - RNA, Small Interfering
KW - Receptors, Neuropeptide
KW - Thinness
KW - Yohimbine
U2 - 10.1086/518445
DO - 10.1086/518445
M3 - Journal article
C2 - 17503329
VL - 80
SP - 1115
EP - 1124
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -
ID: 38454975