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

doi:10.1371/journal.pone.0006696

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

54 Citations (Scopus)

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.

Original language	English
Journal	PLoS ONE
Volume	4
Issue number	8
Pages (from-to)	e6696
Number of pages	8
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0006696
Publication status	Published - 2009

Keywords

Catechol O-Methyltransferase
Diabetes Mellitus, Type 2
Glucose Tolerance Test
Humans
Male
Middle Aged
Obesity
Phenotype
Polymorphism, Single Nucleotide
Receptor, Serotonin, 5-HT2A
Receptor, Serotonin, 5-HT2C

UN SDGs

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

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10.1371/journal.pone.0006696

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724686/pdf/pone.0006696.pdf

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@article{b49cd7a0909811de8bc9000ea68e967b,

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.",

keywords = "Catechol O-Methyltransferase, Diabetes Mellitus, Type 2, Glucose Tolerance Test, Humans, Male, Middle Aged, Obesity, Phenotype, Polymorphism, Single Nucleotide, Receptor, Serotonin, 5-HT2A, Receptor, Serotonin, 5-HT2C",

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}",

note = "Keywords: Catechol O-Methyltransferase; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Male; Middle Aged; Obesity; Phenotype; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C",

year = "2009",

doi = "10.1371/journal.pone.0006696",

language = "English",

volume = "4",

pages = "e6696",

journal = "PLoS Computational Biology",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "8",

}

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

N1 - Keywords: Catechol O-Methyltransferase; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Male; Middle Aged; Obesity; Phenotype; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C

PY - 2009

Y1 - 2009

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.

KW - Catechol O-Methyltransferase

KW - Diabetes Mellitus, Type 2

KW - Glucose Tolerance Test

KW - Humans

KW - Male

KW - Middle Aged

KW - Obesity

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Receptor, Serotonin, 5-HT2A

KW - Receptor, Serotonin, 5-HT2C

U2 - 10.1371/journal.pone.0006696

DO - 10.1371/journal.pone.0006696

M3 - Journal article

C2 - 19690620

SN - 1932-6203

VL - 4

SP - e6696

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 8

ER -

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

Abstract

Keywords

UN SDGs

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