Tomaszewski Maciej, Charchar Fadi J, Lacka Beata, Pesonen Ullamari, Wang William Y S, Zukowska-Szczechowska Ewa, Grzeszczak Wladyslaw, Dominiczak Anna F
British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, University of Glasgow, Western Infirmary, Glasgow G11 6NT, United Kingdom.
Hypertension. 2004 Nov;44(5):689-94. doi: 10.1161/01.HYP.0000143844.81979.61. Epub 2004 Sep 13.
Beta2-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 beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu) and neuropeptide Y (Leu7Pro). Of 3 common haplotypes of beta2-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 beta-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 beta2-adrenergic receptor gene haplotype and provided evidence for epistatic interaction between beta2-adrenergic receptor gene and neuropeptide Y gene in determination of LDL-cholesterol in patients with essential hypertension.
β2-肾上腺素能受体基因和神经肽Y基因可能会对脂质代谢和整体能量平衡产生潜在影响。因此，我们研究了这些基因与高血压患者血脂成分及肥胖相关表型之间的关联。来自212个原发性高血压聚集的波兰家庭的638名白人个体接受了心血管风险决定因素的表型分析。对每个受试者的β2-肾上腺素能受体基因（Arg16Gly和Gln27Glu）和神经肽Y（Leu7Pro）的功能多态性进行基因分型。在β2-肾上腺素能受体基因的3种常见单倍型中，Arg16Gln27过度传递给总胆固醇水平升高（Z=2.2；P=0.026）和低密度脂蛋白胆固醇水平升高（Z=3.2；P=0.002）的后代。单独来看，在基于家系的检测或病例对照分析中，Leu7Pro与任何代谢表型均无关联。然而在存在Arg16Gly的Arg等位基因和Gln27Glu的Gln等位基因的情况下，Leu7Pro多态性的Leu变异纯合子与高血压患者低密度脂蛋白升高的比值比增加2.1倍相关（置信区间为1.10至3.81；P=0.024），独立于年龄、性别、体重指数、血压调整值、抗高血压治疗以及非选择性β受体阻滞剂和利尿剂的使用。同样，在低密度脂蛋白升高的高血压先证者（病例组；P=0.028）中，Arg16Gly、Gln27Glu和Leu7Pro变异之间存在显著的多位点关联，而在低密度脂蛋白正常的高血压受试者（对照组）中则不存在。本研究揭示了低密度脂蛋白胆固醇与β2-肾上腺素能受体基因单倍型之间的关联，并为原发性高血压患者中β2-肾上腺素能受体基因与神经肽Y基因在决定低密度脂蛋白胆固醇水平时的上位相互作用提供了证据。
