Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Xu, Ke; Ma, Lu; Li, Yang; Wang, Fang; Zheng, Gu-Yan; Sun, Zhijun; Jiang, Feng; Chen, Yundai; Liu, Huirong; Dang, Aimin; Chen, Xi; Chun, Jerold; Tian, Xiao-Li
• Is Part Of: Hypertension. Volume 66:Issue 3(2015:Sep.)
• Publication Date: 2015-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.115.05515
• Languages: English
• ISSNs: 0194-911X

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Essential hypertension is a complex disease affected by genetic and environmental factors and serves as a major risk factor for cardiovascular diseases. Serum lysophosphatidic acid correlates with an elevated blood pressure in rats, and lysophosphatidic acid interacts with 6 subtypes of receptors. In this study, we assessed the genetic association of lysophosphatidic acid receptors with essential hypertension by genotyping 28 single-nucleotide polymorphisms from genes encoding for lysophosphatidic acid receptors, <italic>LPAR1</italic>, <italic>LPAR2</italic>, <italic>LPAR3</italic>, <italic>LPAR4</italic>, <italic>LPAR5</italic>, and <italic>LPAR6</italic> and their flanking sequences, in 3 Han Chinese cohorts consisting of 2630 patients and 3171 controls in total. We identified a single-nucleotide polymorphism, rs531003 in the 3′-flanking genomic region of <italic>LPAR1</italic>, associated with hypertension (the Bonferroni corrected <italic>P</italic>=1.09×10<sup>–5</sup>, odds ratio [95% confidence interval]=1.23 [1.13–1.33]). The risk allele C of rs531003 is associated with the increased expression of <italic>LPAR1</italic> and the susceptibility of hypertension, particularly in those with a shortage of sleep (<italic>P</italic>=4.73×10<sup>–5</sup>, odds ratio [95% confidence interval]=1.75 [1.34–2.28]). We further demonstrated that blood pressure elevation caused by sleep deprivation and phenylephrine-induced vasoconstriction was both diminished in <italic>LPAR1</italic>-deficient mice. Together, we show that <italic>LPAR1</italic> is a novel susceptibility gene for human essential hypertension and that stress, such as shortage of sleep, increases the susceptibility of patients with risk allele to essential hypertension.</p> </sec> </abstract>