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Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels
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Zhang, Y., Smith, Edward M., Baye, T. M., Eckert, J. V., Abraham, L. J., Moses, E. K., Kissebah, A. H., Martin, L. J. and Olivier, M. (2010) Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels. Physiological Genomics, 42 (2). pp. 168-176. doi:10.1152/physiolgenomics.00038.2010
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Official URL: http://dx.doi.org/10.1152/physiolgenomics.00038.20...
Abstract
Neurotransmitters such as serotonin (5-hydroxytryptamine, 5-HT) work closely with leptin and insulin to fine-tune the metabolic and neuroendocrine responses to dietary intake. Losing the sensitivity to excess food intake can lead to obesity, diabetes, and a multitude of behavioral disorders. It is largely unclear how different serotonin receptor subtypes respond to and integrate metabolic signals and which genetic variations in these receptor genes lead to individual differences in susceptibility to metabolic disorders. In an obese cohort comprised of families of Northern European descent (n=2,209), the serotonin type 5A receptor gene, HTR5A, was identified as a prominent factor affecting plasma levels of triglycerides, supported by our data from both genome-wide linkage and targeted association analyses using 28 publicly available and 12 newly discovered single nucleotide polymorphisms (SNPs), of which 3 were strongly associated with plasma triglyceride levels (p<0.00125). Bayesian quantitative trait nucleotide (BQTN) analysis identified a putative causal promoter SNP (rs3734967) with substantial posterior probability (p=0.59). Functional analysis of rs3734967 by electrophoretic mobility shift assay (EMSA) showed distinct binding patterns of the two alleles of this SNP with nuclear proteins from glioma cell lines. In conclusion, sequence variants in HTR5A are strongly associated with high plasma levels of triglycerides in a northern European population, suggesting a novel role of the serotonin receptor system in humans. This suggests a potential brain-specific regulation of plasma triglyceride levels, possibly by altering the expression of HTR5A.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Triglycerides , Serotonin, Leptin , Insulin , Ingestion, Obesity, Diabetes , Metabolism -- Disorders | ||||
| Journal or Publication Title: | Physiological Genomics | ||||
| Publisher: | American Physiological Society | ||||
| ISSN: | 1094-8341 | ||||
| Official Date: | 13 April 2010 | ||||
| Dates: |
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| Volume: | 42 | ||||
| Number: | 2 | ||||
| Number of Pages: | 10 | ||||
| Page Range: | pp. 168-176 | ||||
| DOI: | 10.1152/physiolgenomics.00038.2010 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | National Heart, Lung, and Blood Institute | ||||
| Grant number: | HL-74168 |
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