Yatabe Junichi, Yatabe Midori S, Yoneda Minoru, Felder Robin A, Jose Pedro A, Sanada Hironobu
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University, School of Medicine, 1 Hikarigaoka Fukushima, Fukushima 960-1295, Japan.
Int J Hypertens. 2012;2012:806810. doi: 10.1155/2012/806810. Epub 2012 Feb 21.
G protein-coupled receptor kinase 4 (GRK4) with activating polymorphisms desensitize the natriuric renal tubular D1 dopamine receptor, and these GRK4 polymorphisms are strongly associated with salt sensitivity and hypertension. Meanwhile, N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be useful in detecting slight volume expansion. However, relations between hypertension-related gene polymorphisms including GRK4 and cardiovascular indices such as NT-proBNP are not clear, especially in healthy subjects. Therefore, various hypertension-related polymorphisms and cardiovascular indices were analyzed in 97 normotensive, healthy Japanese adults. NT-proBNP levels were significantly higher in subjects with two or more GRK4 polymorphic alleles. Other hypertension-related gene polymorphisms, such as those of renin-angiotensin-aldosterone system genes, did not correlate with NT-proBNP. There was no significant association between any of the hypertension-related gene polymorphisms and central systolic blood pressure, cardioankle vascular index, augmentation index, plasma aldosterone concentration, or an oxidative stress marker, urinary 8-OHdG. Normotensive individuals with GRK4 polymorphisms show increased serum NT-proBNP concentration and may be at a greater risk of developing hypertension and cardiovascular disease.
具有激活多态性的G蛋白偶联受体激酶4(GRK4)会使钠尿性肾小管D1多巴胺受体脱敏,并且这些GRK4多态性与盐敏感性和高血压密切相关。同时,N端前B型利钠肽(NT-proBNP)可能有助于检测轻微的容量扩张。然而,包括GRK4在内的高血压相关基因多态性与NT-proBNP等心血管指标之间的关系尚不清楚,尤其是在健康受试者中。因此,对97名血压正常的健康日本成年人进行了各种高血压相关多态性和心血管指标的分析。具有两个或更多GRK4多态性等位基因的受试者的NT-proBNP水平显著更高。其他高血压相关基因多态性,如肾素-血管紧张素-醛固酮系统基因的多态性,与NT-proBNP无关。任何高血压相关基因多态性与中心收缩压、心踝血管指数、增强指数、血浆醛固酮浓度或氧化应激标志物尿8-羟基脱氧鸟苷之间均无显著关联。具有GRK4多态性的血压正常个体血清NT-proBNP浓度升高,可能有更高的患高血压和心血管疾病的风险。