Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes

Sofia I I Kring, Thomas Werge, Claus Holst, Søren Toubro, Arne Astrup, Torben Hansen, Oluf Pedersen, Thorkild I A Sørensen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2009-null
OriginalsprogEngelsk
TidsskriftPLoS ONE
Vol/bind4
Udgave nummer8
Sider (fra-til)e6696
ISSN1932-6203
DOI
StatusUdgivet - 1. jan. 2009

Fingeraftryk

Receptor, Serotonin, 5-HT2C
Receptor, Serotonin, 5-HT2A
Medical problems
Polymorphism
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
obesity
Genes
genetic polymorphism
Glucose
Glucose Intolerance
genotype
glucose tolerance
genes
norepinephrine
dopamine
serotonin
single nucleotide polymorphism
glucose
Single Nucleotide Polymorphism

Citer dette

Kring, S. I. I., Werge, T., Holst, C., Toubro, S., Astrup, A., Hansen, T., ... Sørensen, T. I. A. (2009). Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes. PLoS ONE, 4(8), e6696. https://doi.org/10.1371/journal.pone.0006696
Kring, Sofia I I ; Werge, Thomas ; Holst, Claus ; Toubro, Søren ; Astrup, Arne ; Hansen, Torben ; Pedersen, Oluf ; Sørensen, Thorkild I A. / Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes. I: PLoS ONE. 2009 ; Bind 4, Nr. 8. s. e6696.
@article{34cf5800feab11deaefb000ea68e967b,
title = "Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes",
abstract = "BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2)) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR = 1.08, CI = 1.01-1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR = 4.56, CI = 1.13-18.4) and acute insulin response (OR = 0.65, CI = 0.44-0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR = 1.04, CI = 1.00-1.09). Except for an association between 5HT2A rs6311 and total-cholesterol at both surveys, significant in S-46 (OR = 2.66, CI = 1.11-6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR = 1.12, CI = 1.03-1.21), fat-BMI (OR = 1.22, CI = 1.08-1.38), waist (OR = 1.13, CI = 1.04-1.22), and cholesterol (OR = 5.60, CI = 0.99-31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3{\%} increased frequency of 5HT2C rs3813929 T-allele and an 11.6{\%} increased frequency of COMT rs4680 GG-genotype in individuals with IGT or T2D (chi(2), p = 0.05 and p = 0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0{\%} increased frequency of IGT or T2D (chi(2), p = 0.01). CONCLUSIONS: The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.",
author = "Kring, {Sofia I I} and Thomas Werge and Claus Holst and S{\o}ren Toubro and Arne Astrup and Torben Hansen and Oluf Pedersen and S{\o}rensen, {Thorkild I A}",
year = "2009",
month = "1",
day = "1",
doi = "10.1371/journal.pone.0006696",
language = "English",
volume = "4",
pages = "e6696",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
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}

Kring, SII, Werge, T, Holst, C, Toubro, S, Astrup, A, Hansen, T, Pedersen, O & Sørensen, TIA 2009, 'Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes', PLoS ONE, bind 4, nr. 8, s. e6696. https://doi.org/10.1371/journal.pone.0006696

Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes. / Kring, Sofia I I; Werge, Thomas; Holst, Claus; Toubro, Søren; Astrup, Arne; Hansen, Torben; Pedersen, Oluf; Sørensen, Thorkild I A.

I: PLoS ONE, Bind 4, Nr. 8, 01.01.2009, s. e6696.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Polymorphisms of serotonin receptor 2A and 2C genes and COMT in relation to obesity and type 2 diabetes

AU - Kring, Sofia I I

AU - Werge, Thomas

AU - Holst, Claus

AU - Toubro, Søren

AU - Astrup, Arne

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Sørensen, Thorkild I A

PY - 2009/1/1

Y1 - 2009/1/1

N2 - BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2)) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR = 1.08, CI = 1.01-1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR = 4.56, CI = 1.13-18.4) and acute insulin response (OR = 0.65, CI = 0.44-0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR = 1.04, CI = 1.00-1.09). Except for an association between 5HT2A rs6311 and total-cholesterol at both surveys, significant in S-46 (OR = 2.66, CI = 1.11-6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR = 1.12, CI = 1.03-1.21), fat-BMI (OR = 1.22, CI = 1.08-1.38), waist (OR = 1.13, CI = 1.04-1.22), and cholesterol (OR = 5.60, CI = 0.99-31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GG-genotype in individuals with IGT or T2D (chi(2), p = 0.05 and p = 0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0% increased frequency of IGT or T2D (chi(2), p = 0.01). CONCLUSIONS: The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.

AB - BACKGROUND: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2)) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR = 1.08, CI = 1.01-1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR = 4.56, CI = 1.13-18.4) and acute insulin response (OR = 0.65, CI = 0.44-0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR = 1.04, CI = 1.00-1.09). Except for an association between 5HT2A rs6311 and total-cholesterol at both surveys, significant in S-46 (OR = 2.66, CI = 1.11-6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR = 1.12, CI = 1.03-1.21), fat-BMI (OR = 1.22, CI = 1.08-1.38), waist (OR = 1.13, CI = 1.04-1.22), and cholesterol (OR = 5.60, CI = 0.99-31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GG-genotype in individuals with IGT or T2D (chi(2), p = 0.05 and p = 0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0% increased frequency of IGT or T2D (chi(2), p = 0.01). CONCLUSIONS: The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.

U2 - 10.1371/journal.pone.0006696

DO - 10.1371/journal.pone.0006696

M3 - Journal article

VL - 4

SP - e6696

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 8

ER -