Association between a dopamine-4 receptor polymorphism and blood pressure.
Association between a dopamine-4 receptor polymorphism and blood pressure.
复制标题
多巴胺 4 受体多态性与血压之间的关联。
DOI：
10.1016/j.amjhyper.2005.04.010
复制
发表时间：
2005
影响因子：
3.2
通讯作者：
Weder,AlanB
中科院分区：
文献类型：
--
作者：
Sen,Srijan;Nesse,Randolph;Sheng,Li;Stoltenberg,ScottF;Gleiberman,Lillian;Burmeister,Margit;Weder,AlanB
背景：多巴胺受体基因是高血压易感性的候选基因。局部释放的多巴胺增加肾脏钠排泄，并且已证明肾脏多巴胺受体信号传导缺陷在高血压中发挥作用。多巴胺-4受体在肾小球和皮质集合细胞中表达，其中多巴胺活化可改变钠和水代谢并影响血压（BP）。多巴胺-4受体（DRD 4）基因具有位于外显子3的16个氨基酸（48个碱基对[bp]）重复多态性，其中编码G蛋白结合区。长等位基因（定义为至少有一个7到10个重复）与人格特质新奇寻求和物质滥用有关，但多巴胺-4受体多态性与BP之间的关联尚未报道。方法：我们对白色种族的479名女性和385名男性受试者在DRD 4重复多态性位点进行基因分型，并将每个受试者分为长或短基因型。我们发现DRD 4长等位基因和收缩压升高之间存在关联（P= 0.031），舒张压（P= 0.034），和经常饮酒史（P= 0.008）。此外，收缩压（P= 0.009）和脉压（P= 0.002），我们发现多巴胺-4受体等位基因和年龄之间的相互作用的证据，表明多巴胺-4受体变异体对BP的影响随着年龄的增长而增加。结论：在这个白色人群中，DRD 4基因的长变异体与3毫米汞柱高收缩压和2毫米汞柱高舒张压相关。Am J Hypertens 2005;18：1206-1210 © 2005 American Journal of Hypertension，Ltd.
Background:Dopamine receptor genes are candidates for hypertension susceptibility. Locally released dopamine increases renal sodium excretion, and defective renal dopamine receptor signaling has been shown to play a role in hypertension. Dopamine-4 receptors are expressed in juxtaglomerular and cortical collecting cells, where dopamine activation could alter sodium and water metabolism and affect blood pressure (BP). The dopamine-4 receptor (DRD4) gene has a 16 amino acid (48 base pairs [bp]) repeat polymorphism located in exon 3 where a G-protein binding area is encoded. The long allele (defined as at least one 7 to 10 repeat) has been associated with the personality trait Novelty Seeking and with substance abuse, but associations between dopamine-4 receptor polymorphisms and BP have not been reported.Methods:We genotyped 479 female and 385 male subjects of white ethnicity at the DRD4 repeat polymorphism site and classified each subject as having either the long or short genotype.Results:We found associations between the DRD4 long allele and increased systolic BP (P= .031), diastolic BP (P= .034), and a history of regular alcohol use (P= .008). Furthermore, for systolic BP (P= .009) and pulse pressure (P= .002), we found evidence for an interaction between dopamine-4 receptor alleles and age, indicating that the effects of dopamine-4 receptor variants on BP increase with age.Conclusion:In this white population, the long variant of the DRD4 gene is associated with a 3–mm Hg higher systolic and 2–mm Hg higher diastolic BP. Am J Hypertens 2005;18:1206–1210 © 2005 American Journal of Hypertension, Ltd.