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Published on: September 23, 2015
Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels
1Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Physiological Genomics
|April 15, 2010
Summary
Genetic variations in the serotonin receptor gene HTR5A are linked to higher triglyceride levels in a Northern European population. This suggests HTR5A may play a role in brain-based regulation of plasma triglycerides.
Area of Science:
- Neuroscience
- Genetics
- Metabolic Disorders
Background:
- Serotonin (5-hydroxytryptamine, 5-HT) interacts with leptin and insulin to regulate metabolic and neuroendocrine functions.
- Reduced sensitivity to food intake can lead to obesity, diabetes, and behavioral issues.
- The role of specific serotonin receptor subtypes in integrating metabolic signals and genetic influences on metabolic disorder susceptibility remains unclear.
Purpose of the Study:
- To investigate the association between serotonin receptor gene variants and plasma triglyceride levels.
- To identify specific genetic variations in HTR5A influencing metabolic traits.
- To explore the functional impact of identified genetic variants on HTR5A expression and regulation.
Main Methods:
- Genome-wide linkage and targeted association analyses were performed on a cohort of 2,209 individuals of Northern European descent.
- 28 publicly available and 12 newly discovered single nucleotide polymorphisms (SNPs) in HTR5A were analyzed.
- Bayesian quantitative trait nucleotide (BQTN) analysis and electrophoretic mobility shift assays (EMSA) were used for SNP analysis and functional validation.
Main Results:
- The serotonin type 5A receptor gene (HTR5A) was identified as a significant factor influencing plasma triglyceride (TG) levels.
- Three SNPs in HTR5A showed strong association with plasma TG levels (P < 0.00125).
- A putative causal promoter SNP (rs3734967) was identified, with distinct nuclear protein binding patterns observed for its alleles via EMSA.
Conclusions:
- Sequence variants in HTR5A are strongly associated with elevated plasma TG levels in a Northern European population.
- This finding suggests a novel role for the serotonin receptor system in human metabolic regulation.
- The results indicate a potential brain-specific regulation of plasma TG levels, possibly mediated by altered HTR5A expression.
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