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Polymorphisms of Serotonin Receptor 2A and 2C Genes and COMT in Relation to Obesity and Type 2 Diabetes
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 ge...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724686/ https://www.ncbi.nlm.nih.gov/pubmed/19690620 http://dx.doi.org/10.1371/journal.pone.0006696 |
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author | Kring, Sofia I. I. Werge, Thomas Holst, Claus Toubro, Søren Astrup, Arne Hansen, Torben Pedersen, Oluf Sørensen, Thorkild I. A. |
author_facet | Kring, Sofia I. I. Werge, Thomas Holst, Claus Toubro, Søren Astrup, Arne Hansen, Torben Pedersen, Oluf Sørensen, Thorkild I. A. |
author_sort | Kring, Sofia I. I. |
collection | PubMed |
description | 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≥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 (χ(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 (χ(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. |
format | Text |
id | pubmed-2724686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27246862009-08-19 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. PLoS One Research Article 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≥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 (χ(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 (χ(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. Public Library of Science 2009-08-19 /pmc/articles/PMC2724686/ /pubmed/19690620 http://dx.doi.org/10.1371/journal.pone.0006696 Text en Kring et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 |
title | Polymorphisms of Serotonin Receptor 2A and 2C Genes and COMT in Relation to Obesity and Type 2 Diabetes |
title_full | Polymorphisms of Serotonin Receptor 2A and 2C Genes and COMT in Relation to Obesity and Type 2 Diabetes |
title_fullStr | Polymorphisms of Serotonin Receptor 2A and 2C Genes and COMT in Relation to Obesity and Type 2 Diabetes |
title_full_unstemmed | Polymorphisms of Serotonin Receptor 2A and 2C Genes and COMT in Relation to Obesity and Type 2 Diabetes |
title_short | Polymorphisms of Serotonin Receptor 2A and 2C Genes and COMT in Relation to Obesity and Type 2 Diabetes |
title_sort | polymorphisms of serotonin receptor 2a and 2c genes and comt in relation to obesity and type 2 diabetes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724686/ https://www.ncbi.nlm.nih.gov/pubmed/19690620 http://dx.doi.org/10.1371/journal.pone.0006696 |
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