A screen of candidate genes and influence of β2-adrenergic receptor genotypes in postural tachycardia syndrome
| Autor: | Kim K. Nickander, Michael Camilleri, Raul Urrutia, Phillip A. Low, Paula Carlson |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Tachycardia Candidate gene medicine.medical_specialty Genotype Arginine Posture Blood Pressure Single-nucleotide polymorphism Polymorphism Single Nucleotide Denaturing high performance liquid chromatography Cellular and Molecular Neuroscience Heart Rate Internal medicine medicine Humans Genetic Testing Electron Transport Complex I Norepinephrine Plasma Membrane Transport Proteins Symporters biology Endocrine and Autonomic Systems Middle Aged Glutamine Endocrinology Norepinephrine transporter biology.protein Female Receptors Adrenergic beta-2 Neurology (clinical) Orthostatic tachycardia medicine.symptom |
| Zdroj: | Autonomic Neuroscience. 120:97-103 |
| ISSN: | 1566-0702 |
| DOI: | 10.1016/j.autneu.2005.05.001 |
| Popis: | Objective To screen candidate genes, encoding β 2 -adrenergic receptor (β 2 AR), α 2C -adrenergic receptor (α 2C AR), norepinephrine transporter (NET), and mitochondrial complex I (COI), for common single nucleotide polymorphisms (SNPs) in patients with postural tachycardia syndrome (POTS); alterations could potentially cause or aggravate orthostatic tachycardia and to relate β 2 AR SNPs, known to effect venomotor tone, to heart rate (HR) and blood pressure measurements during 10-min head-up tilt. Methods (a) DNA extraction from leukocytes of 29 patients with POTS; (b) Denaturing high performance liquid chromatography analysis to screen for the 12-bp deletion (Del322–325) in α 2C AR and for the alanine to proline mutation at amino acid 457 (Ala457Pro ) in NET; (c) Systematic direct sequence analysis to screen for SNPs in β 2 AR, NET, and COI. Results Three common polymorphisms were abundant in at least one allele in β 2 AR resulting in a cysteine to arginine in the 5′ promoter region (72% of patients), an arginine to glycine at amino acid-16 (Gly16; 86%), and a glutamine to glutamic acid at amino acid-27 (Glu27; 66%), a frequency that was no different to the normal Caucasian population. Orthostatic HR was significantly greater in patients with Glu27. Diastolic blood pressure (DBP) was significantly lower in a subset of patients with Gly16 whose HR were ≥ 120 beats/min with head-up tilt. All patients did not show the Ala457Pro mutation of NET; all sequence variants detected in α 2C AR, NET, and COI were not considered causally related to POTS. Conclusions Of the candidate genes screened, none harbored a SNP considered to be causally related to POTS. There was significant association of HR and DBP with SNPs of the gene encoding β 2 AR; Gly16 or Glu27 could aggravate orthostatic tachycardia by excessive venous pooling. |
| Databáze: | OpenAIRE |
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