Published online before print September 13, 2004, doi: 10.1161/01.HYP.0000143844.81979.61
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(Hypertension. 2004;44:689.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
Epistatic Interaction Between ß2-Adrenergic Receptor and Neuropeptide Y Genes Influences LDL-Cholesterol in Hypertension
From the British Heart Foundation Glasgow Cardiovascular Research Centre (M.T., F.J.C., A.F.D.), Division of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom; Department of Internal Medicine (M.T., B.L., E.Z-S., W.G.), Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland; Department of Pharmacology and Clinical Pharmacology (U.P.), University of Turku, Finland; and Department of Medical Genetics (W.Y.S.W.), University of Cambridge, United Kingdom.
Correspondence to Dr Maciej Tomaszewski, British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary Glasgow G11 6NT UK. E-mail mt65h{at}clinmed.gla.ac.uk
ß2-Adrenergic receptor gene and neuropeptide Y gene may potentially influence lipid metabolism and overall energy balance. Therefore, we examined associations of these genes with lipid fractions and obesity-related phenotypes in hypertensive subjects. A total of 638 white individuals from 212 Polish families with clustering of essential hypertension were phenotyped for cardiovascular risk determinants. Each subject was genotyped for functional polymorphisms of ß 2-adrenergic receptor gene (Arg16Gly and Gln27Glu) and neuropeptide Y (Leu7Pro). Of 3 common haplotypes of ß2-adrenergic receptor gene, Arg16Gln27 was overtransmitted to offspring with elevated levels of total cholesterol (Z=2.2; P=0.026) and LDL-cholesterol (Z=3.2; P=0.002). Individually, Leu7Pro was not associated with any of the metabolic phenotypes in family-based tests or case-control analyses. However, in the presence of Arg allele of Arg16Gly and Gln allele of Gln27Glu, homozygosity for Leu variant of the Leu7Pro polymorphism was associated with 2.1-increased odds ratio (confidence interval, 1.10 to 3.81; P=0.024) of elevated LDL in hypertensive subjects, independent of age, gender, body mass index, adjusted blood pressures, antihypertensive therapy, and use of nonselective ß-blockers and diuretics. Consistently, there was a significant multilocus association among variants of Arg16Gly, Gln27Glu, and Leu7Pro in hypertensive probands with elevated LDL (cases; P=0.028) but not in hypertensive subjects with normal LDL (controls). This study revealed an association of LDL-cholesterol with ß 2-adrenergic receptor gene haplotype and provided evidence for epistatic interaction between ß2-adrenergic receptor gene and neuropeptide Y gene in determination of LDL-cholesterol in patients with essential hypertension.
Key Words: receptors, adrenergic • neuropeptide Y • genes • cholesterol
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