Tomaszewski, M., Charchar, F., Lacka, B., Pesonen, U., Wang, W., Zukowska-Szczechowska, E., Grzeszczak, W. and Dominiczak, A. (2004) Epistatic interaction between beta2-adrenergic receptor and neuropeptide Y genes influences LDL-cholesterol in hypertension. Hypertension, 44(5), pp. 689-694. (doi: 10.1161/01.HYP.0000143844.81979.61)
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Abstract
β2-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 β 2-adrenergic receptor gene (Arg16Gly and Gln27Glu) and neuropeptide Y (Leu7Pro). Of 3 common haplotypes of β2-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 β-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 β 2-adrenergic receptor gene haplotype and provided evidence for epistatic interaction between β2-adrenergic receptor gene and neuropeptide Y gene in determination of LDL-cholesterol in patients with essential hypertension.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dominiczak, Professor Anna |
| Authors: | Tomaszewski, M., Charchar, F., Lacka, B., Pesonen, U., Wang, W., Zukowska-Szczechowska, E., Grzeszczak, W., and Dominiczak, A. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Hypertension |
| Publisher: | American Heart Association |
| ISSN: | 0194-911X |
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