Serum autotaxin measurements in pregnant women: Application for the differentiation of normal pregnancy and pregnancy-induced hypertension

Masuda, Akiko; Fujii, Tomoyuki; Iwasawa, Yuki; Nakamura, Kazuhiro; Ohkawa, Ryunosuke; Igarashi, Koji; Okudaira, Shinichi; Ikeda, Hitoshi; Kozuma, Shiro; Aoki, Junken; Yatomi, Yutaka

doi:10.1016/j.cca.2011.06.039

Cited by 47 publications

(33 citation statements)

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“…We previously reported that the concentration of serum total ATX antigen in patients with CLD and FL was significantly higher than that in healthy subjects [5,15], and the serum total ATX level was significantly higher in normal pregnant females than in non-pregnant healthy females [17]. Therefore, we next measured the concentrations of classical ATX and novel ATX antigens in sera from normal pregnant women and patients with CLD, FL, or DM.…”

Section: Resultsmentioning

confidence: 99%

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A New Enzyme Immunoassay for the Quantitative Determination of Classical Autotaxins (ATXα, ATXβ, and ATXγ) and Novel Autotaxins (ATXδ and ATXε)

et al. 2015

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BackgroundAutotaxin (ATX) is a secreted enzyme that converts lysophosphatidylcholine to lysophosphatidic acid, a potent bioactive lipid mediator, through its lysophospholipase D activity. Although five alternative splicing isoforms of ATX have been identified as ATXα, ATXβ, ATXγ, ATXδ, and ATXε and the expression patterns of each isoform differ among several tissues, the clinical significance of each isoform remains to be elucidated.MethodsAnti-ATXβ and anti-ATXδ monoclonal antibodies were produced by immunization with recombinant human ATXβ and ATXδ expressed using a baculovirus system, respectively. We then developed enzyme immunoassays to measure the serum concentrations of “classical ATX” (ATXα, ATXβ, and ATXγ) and “novel ATX” (ATXδ and ATXε) antigens and evaluated the usefulness of these assays using human serum samples.ResultsThe with-run and between-run precision, interference, detection limit, and linearity studies for the present assay were well validated. In healthy subjects, the serum concentrations of classical ATX and novel ATX were significantly (P < 0.01) higher in women than in men, while the ratios of classical ATX or novel ATX to total ATX were not different between women and men. The concentrations of both classical ATX and novel ATX in normal pregnant subjects and patients with chronic liver diseases or follicular lymphoma were significantly higher than those in healthy subjects, while the ratio of both ATX isoforms to total ATX did not vary among these groups.ConclusionsWe have developed a new enzyme immunoassay to determine the concentrations of classical ATX and novel ATX in human serum. These assays may be helpful for elucidating the distinct functional roles of each ATX isoform, which are largely unknown at present.

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Section: Resultsmentioning

confidence: 99%

“…Regarding the clinical significance of ATX, the concentration of serum ATX antigen was reportedly elevated in patients with chronic liver diseases (CLD) [5], follicular lymphoma (FL) [15], and pancreatic cancer [16] and was significantly higher in normal pregnant females than in non-pregnant healthy females [17]. …”

Section: Introductionmentioning

confidence: 99%

A New Enzyme Immunoassay for the Quantitative Determination of Classical Autotaxins (ATXα, ATXβ, and ATXγ) and Novel Autotaxins (ATXδ and ATXε)

et al. 2015

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“…During pregnancy, ATX concentration is upregulated in the serum and placenta of healthy women in the third trimester. Interestingly, patients with pregnancyinduced hypertension (preeclampsia) harbored decreased ATX levels in the third trimester compared with healthy women (56,167,168). LPA receptors are also expressed in the testis (19,77,88), suggesting a role for LPA signaling in male sperm behavior and fertility.…”

Section: Lpamentioning

confidence: 99%

LPA receptor signaling: pharmacology, physiology, and pathophysiology

Yung

Stoddard

Chun

2014

Journal of Lipid Research

592

683

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“…17 Human hypertensive patients have higher levels of LPA 19 and autotaxin (a main producer of serum/plasma LPA). 22 However, it remains unknown whether or not genetic variants of LPA receptors in humans are associated with EH.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension

et al. 2015

Hypertension

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Abstract-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, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 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 LPAR1, associated with hypertension (the Bonferroni corrected P=1.09×10 -5 , odds ratio [95% confidence interval]=1.23 [1.13-1.33]). The risk allele C of rs531003 is associated with the increased expression of LPAR1 and the susceptibility of hypertension, particularly in those with a shortage of sleep (P=4.73×10 -5 , 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 LPAR1-deficient mice. Together, we show that LPAR1 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. Results Characteristics of PopulationsTwo thousand six hundred thirty patients with EH and 3171 controls of Han Chinese were recruited from 3 geographically independent medical centers in total. The characteristics of these populations are shown in Table 1. In addition to the prevalence of coronary artery disease and diabetes mellitus, the biochemical parameters were significantly different between case and control groups at each center. Although most of the hypertensive patients were treated with antihypertensive drugs, the SBP and diastolic blood pressure remained higher compared with their counterparts (Table 1). Single-Nucleotide Polymorphism Association TestTwenty-nine single-nucleotide polymorphisms (SNPs) from the LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 genes and their flanking sequences were first genotyped in population 1 by multiplex ligation-dependent probe amplification. Twenty-eight SNPs were genotyped successfully. The 28 SNPs are shown in Table S5. The primers used for multiplex ligation-dependent probe amplification and sequencing are listed in Tables S2 and S3. The consistency between 2 genotyping methods was generally >99%. All SNPs passed the Hardy-Weinberg equilibrium test (Table S5). In allelic association analysis, 2 SNPs in the LPAR1 gene, rs2766997 (P=0.037) and rs531003 (P=0.006), exhibited positive signals (P<0.05) associated with EH in population 1 in the regression test adjusted risk factors, including sex, age, body mass index, and diabetes mellitus (Tabl...

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Serum autotaxin measurements in pregnant women: Application for the differentiation of normal pregnancy and pregnancy-induced hypertension

Cited by 47 publications

References 42 publications

A New Enzyme Immunoassay for the Quantitative Determination of Classical Autotaxins (ATXα, ATXβ, and ATXγ) and Novel Autotaxins (ATXδ and ATXε)

A New Enzyme Immunoassay for the Quantitative Determination of Classical Autotaxins (ATXα, ATXβ, and ATXγ) and Novel Autotaxins (ATXδ and ATXε)

LPA receptor signaling: pharmacology, physiology, and pathophysiology

Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension

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