A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis

Ingrid Dahlman; Andrea Dicker; Hong Jiao; Juha Kere; Lennart Blomqvist; Vanessa van Harmelen; Johan Hoffstedt; Knut Borch-Johnsen; Torben Jorgensen; Torben Hansen; Oluf Pedersen; Markku Laakso; Peter Arner

doi:10.1086/518445

A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis

Ingrid Dahlman, Andrea Dicker, Hong Jiao, Juha Kere, Lennart Blomqvist, Vanessa van Harmelen, Johan Hoffstedt, Knut Borch-Johnsen, Torben Jorgensen, Torben Hansen, Oluf Pedersen, Markku Laakso, Peter Arner

Department of Public Health

13 Citations (Scopus)

Abstract

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.

Original language	English
Journal	American Journal of Human Genetics
Volume	80
Issue number	6
Pages (from-to)	1115-24
Number of pages	10
ISSN	0002-9297
DOIs	https://doi.org/10.1086/518445
Publication status	Published - 2007

Keywords

Adipocytes
Adrenergic alpha-Agonists
Adrenergic alpha-Antagonists
Adult
Alleles
Bucladesine
Cell Differentiation
Cohort Studies
Dose-Response Relationship, Drug
Drug Interactions
Female
Gene Frequency
Haplotypes
Humans
Linkage Disequilibrium
Lipolysis
Male
Middle Aged
Norepinephrine
Odds Ratio
Polymorphism, Single Nucleotide
RNA, Small Interfering
Receptors, Neuropeptide
Thinness
Yohimbine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/518445

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Dahlman, I., Dicker, A., Jiao, H., Kere, J., Blomqvist, L., van Harmelen, V., Hoffstedt, J., Borch-Johnsen, K., Jorgensen, T., Hansen, T., Pedersen, O., Laakso, M., & Arner, P. (2007). A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis. American Journal of Human Genetics, 80(6), 1115-24. https://doi.org/10.1086/518445

Dahlman, I, Dicker, A, Jiao, H, Kere, J, Blomqvist, L, van Harmelen, V, Hoffstedt, J, Borch-Johnsen, K, Jorgensen, T, Hansen, T , Pedersen, O, Laakso, M & Arner, P 2007, 'A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis', American Journal of Human Genetics, vol. 80, no. 6, pp. 1115-24. https://doi.org/10.1086/518445

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title = "A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis",

abstract = "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.",

keywords = "Adipocytes, Adrenergic alpha-Agonists, Adrenergic alpha-Antagonists, Adult, Alleles, Bucladesine, Cell Differentiation, Cohort Studies, Dose-Response Relationship, Drug, Drug Interactions, Female, Gene Frequency, Haplotypes, Humans, Linkage Disequilibrium, Lipolysis, Male, Middle Aged, Norepinephrine, Odds Ratio, Polymorphism, Single Nucleotide, RNA, Small Interfering, Receptors, Neuropeptide, Thinness, Yohimbine",

author = "Ingrid Dahlman and Andrea Dicker and Hong Jiao and Juha Kere and Lennart Blomqvist and {van Harmelen}, Vanessa and Johan Hoffstedt and Knut Borch-Johnsen and Torben Jorgensen and Torben Hansen and Oluf Pedersen and Markku Laakso and Peter Arner",

year = "2007",

doi = "10.1086/518445",

language = "English",

volume = "80",

pages = "1115--24",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

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number = "6",

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TY - JOUR

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

SN - 0002-9297

VL - 80

SP - 1115

EP - 1124

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis

Abstract

Keywords

UN SDGs

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