Genetic variations in hypoxia response genes influence hypertrophic cardiomyopathy phenotype.

Abstract:

BACKGROUND:Risk factors for diastolic dysfunction in hypertrophic cardiomyopathy (HCM) are poorly understood. We investigated the association of variants in hypoxia-response genes with phenotype severity in pediatric HCM. METHODS:A total of 80 unrelated patients <21 y and 14 related members from eight families with HCM were genotyped for six variants associated with vascular endothelial growth factor A (VEGFA) downregulation, or hypoxia-inducible factor A (HIF1A) upregulation. Associations between risk genotypes and left-ventricular (LV) hypertrophy, LV dysfunction, and freedom from myectomy were assessed. Tissue expression was measured in myocardial samples from 17 patients with HCM and 20 patients without HCM. RESULTS:Age at enrollment was 9 ± 5 y (follow-up, 3.1 ± 3.6 y). Risk allele frequency was 67% VEGFA and 92% HIF1A. Risk genotypes were associated with younger age at diagnosis (P < 0.001), septal hypertrophy (P < 0.01), prolonged E-wave deceleration time (EWDT) (P < 0.0001) and isovolumic relaxation time (IVRT) (P < 0.0001), and lower freedom from myectomy (P < 0.05). These associations were seen in sporadic and familial HCM independent of the disease-causing mutation. Risk genotypes were associated with higher myocardial HIF1A and transforming growth factor B1 (TGFB1) expression and increased endothelial-fibroblast transformation (P < 0.05). CONCLUSION:HIF1A-upregulation and/or VEGFA-downregulation genotypes were associated with more severe septal hypertrophy and diastolic dysfunction and may provide genetic markers to improve risk prediction in HCM.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Alkon J,Friedberg MK,Manlhiot C,Manickaraj AK,Kinnear C,McCrindle BW,Benson LN,Addonizio LJ,Colan SD,Mital S

doi

10.1038/pr.2012.126

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

583-92

issue

6

eissn

0031-3998

issn

1530-0447

pii

pr2012126

journal_volume

72

pub_type

杂志文章
  • CD4+ T-cell counts and interleukin-8 and CCL-5 plasma concentrations discriminate disease severity in children with RSV infection.

    abstract:BACKGROUND:Current tools to predict the severity of respiratory syncytial virus (RSV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RSV-infected children. METHODS:Blood and nasopharyng...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2012.163

    authors: Brand HK,Ferwerda G,Preijers F,de Groot R,Neeleman C,Staal FJ,Warris A,Hermans PW

    更新日期:2013-02-01 00:00:00

  • Utilization of D-beta-hydroxybutyrate and oleate as alternate energy fuels in brain cell cultures of newborn mice after hypoxia at different glucose concentrations.

    abstract::In dissociated whole brain cell cultures from newborn mice, we have previously shown that during glucose deprivation under normoxia, D-beta-hydroxybutyrate and oleic acid are increasingly used for energy production. We now asked whether this glucose dependency of the utilization of D-beta-hydroxybutyrate and oleic aci...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198911000-00023

    authors: Bossi E,Kohler E,Herschkowitz N

    更新日期:1989-11-01 00:00:00

  • Evaluation of insulin sensitivity in obese offspring of diabetic rats by hyperinsulinemic-euglycemic clamp technique.

    abstract::Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance i...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199107000-00008

    authors: Gelardi NL,Cha CJ,Oh W

    更新日期:1991-07-01 00:00:00

  • Gestational age, sex and maternal parity correlate with bone turnover in premature infants.

    abstract::Factors affecting bone turnover in premature infants are not entirely clear but certainly are different from those influencing bones of adults and children. To identify fetal and maternal factors that might influence bone turnover, we prospectively studied 50 infants (30 preterm and 20 full-term) born at Ain Shams Uni...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.PDR.0000160591.70409.C8

    authors: Aly H,Moustafa MF,Amer HA,Hassanein S,Keeves C,Patel K

    更新日期:2005-05-01 00:00:00

  • Regional splanchnic oxygen saturation for preterm infants in the first week after birth: reference values.

    abstract:BACKGROUND:Near-infrared spectroscopy is used in the assessment of regional splanchnic oxygen saturation (rsSO2), but solid reference values are scarce. We aimed to establish reference values of rsSO2 for preterm infants during the first week after birth, both crude and modeled based on predictors. METHODS:We included...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-01323-3

    authors: van der Heide M,Dotinga BM,Stewart RE,Kalteren WS,Hulscher JBF,Reijneveld SA,Bos AF,Kooi EMW

    更新日期:2021-01-27 00:00:00

  • Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: a Scandinavian case-cohort study.

    abstract:BACKGROUND:The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the lit...

    journal_title:Pediatric research

    pub_type: 杂志文章,多中心研究

    doi:10.1038/pr.2016.187

    authors: Lauritzen HB,Larose TL,Øien T,Sandanger TM,Odland JØ,van de Bor M,Jacobsen GW

    更新日期:2017-01-01 00:00:00

  • Positive renal response to intravenous acetazolamide in patients with carbonic anhydrase II deficiency.

    abstract::Carbonic anhydrase II (CA II) is the only soluble isozyme of CA which is known to be expressed in kidney. We recently identified a deficiency of this enzyme as the basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. In order to explore the physiological i...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198510000-00017

    authors: Sly WS,Whyte MP,Krupin T,Sundaram V

    更新日期:1985-10-01 00:00:00

  • Retraction Note: Intra-amniotic LPS amplifies hyperoxia-induced airway hyperreactivity in neonatal rats.

    abstract::This paper has been retracted at the request of the authors. ...

    journal_title:Pediatric research

    pub_type: 杂志文章,撤回出版物

    doi:10.1038/s41390-019-0529-y

    authors: Choi CW,Kim BI,Mason SN,Potts-Kant EN,Brahmajothi MV,Auten RL

    更新日期:2019-11-01 00:00:00

  • Contribution of sarcoplasmic reticulum Ca²+ release and Ca²+ transporters on sarcolemmal channels to Ca²+ transient in fetal mouse heart.

    abstract::Sarcoplasmic reticulum (SR) Ca release has been shown not to be the predominant mechanism responsible for excitation-contraction (E-C) coupling in fetal myocytes. However, most of the studies have been conducted either on primary cultures or acutely isolated cells, in which an apparent reduction of ryanodine receptor ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/PDR.0b013e31820bc69b

    authors: Takizawa M,Ishiwata T,Kawamura Y,Kanai T,Kurokawa T,Nishiyama M,Ishida H,Asano Y,Nonoyama S

    更新日期:2011-04-01 00:00:00

  • Effects of prenatal tobacco exposure on gene expression profiling in umbilical cord tissue.

    abstract::Maternal smoking doubles the risk of delivering a low birth weight infant. The purpose of this study was to analyze differential gene expression in umbilical cord tissue as a function of maternal smoking, with an emphasis on growth-related genes. We recruited 15 pregnant smokers and 15 women who never smoked during pr...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/PDR.0b013e31817c5507

    authors: Hussain N,Krueger W,Covault J,Walsh S,Kranzler HR,Oncken C

    更新日期:2008-08-01 00:00:00

  • Reduced free-radical-trapping capacity and altered plasma antioxidant status in cystic fibrosis.

    abstract::Plasma antioxidant status and total radical-trapping antioxidant potential (TRAP) of children (n = 24) with cystic fibrosis (CF) were compared with those of children (n = 21) without the disease. Children with CF were found to have elevated plasma concentrations of ascorbic acid (94.6 +/- 58.2 mumol/L), with respect t...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199303000-00008

    authors: Langley SC,Brown RK,Kelly FJ

    更新日期:1993-03-01 00:00:00

  • Deficient collagen-induced activation in the newborn platelet.

    abstract::We have investigated the impaired secretion response of neonatal platelets. We compared the response of washed neonatal and adult platelets to thrombin and collagen, and to specific activators of calcium flux (inositol trisphosphate) and protein kinase C activation (oleoyl-acetyl glycerol). Neonatal platelets show no ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199004000-00004

    authors: Israels SJ,Daniels M,McMillan EM

    更新日期:1990-04-01 00:00:00

  • Diversity of immunoglobulin light chain usage in the human immune response to Haemophilus influenzae type b capsular polysaccharide.

    abstract::The response to the capsular polysaccharide of Haemophilus influenzae type b (Hib PS) has been used to determine the molecular basis of antibody gene diversity in humans. In contrast to the relatively restricted nature of anti-Hib PS heavy-chain variable region gene expression, a variety of light-chain variable region...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199303000-00022

    authors: Adderson EE,Shackelford PG,Quinn A,Wilson PM,Carroll WL

    更新日期:1993-03-01 00:00:00

  • Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV-1 infection.

    abstract:BACKGROUND:Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low- and middle-income countries. METHODS:Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-...

    journal_title:Pediatric research

    pub_type: 杂志文章,多中心研究

    doi:10.1038/pr.2016.53

    authors: Huerta-García G,Vazquez-Rosales JG,Mata-Marín JA,Peregrino-Bejarano L,Flores-Ruiz E,Solórzano-Santos F

    更新日期:2016-07-01 00:00:00

  • Development of the sleep and wakefulness rhythm in preterm infants discharged from a neonatal care unit.

    abstract::The purpose of this study was to investigate the effect of constant light in a neonatal care unit on the development of the sleep-and-wakefulness rhythm in preterm infants. Two groups of infants (57 preterm infants without other complications and 58 healthy term infants) were prospectively studied over infancy by a da...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199302000-00014

    authors: Shimada M,Segawa M,Higurashi M,Akamatsu H

    更新日期:1993-02-01 00:00:00

  • High-frequency oscillatory ventilation is not associated with increased risk of neuropathology compared with positive pressure ventilation: a preterm primate model.

    abstract::High-frequency oscillatory ventilation (HFOV) may improve pulmonary outcome in very preterm infants, but the effects on the brain are largely unknown. We hypothesized that early prolonged HFOV compared with low volume positive pressure ventilation (LV-PPV) would not increase the risk of delayed brain growth or injury ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/PDR.0b013e3181bb0cc1

    authors: Loeliger M,Inder TE,Shields A,Dalitz P,Cain S,Yoder B,Rees SM

    更新日期:2009-11-01 00:00:00

  • Effect of television viewing at mealtime on food intake after a glucose preload in boys.

    abstract::Television viewing (TVV) is considered a contributing factor to the development of childhood obesity yet it is unclear whether obesity results, in part, from increased energy intake during TVV. The objective of this study was to determine the effect of TVV on food intake (FI) of boys at a meal and its effect on calori...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/pdr.0b013e3180536591

    authors: Bellissimo N,Pencharz PB,Thomas SG,Anderson GH

    更新日期:2007-06-01 00:00:00

  • Endodermal and mesenchymal cross talk: a crossroad for the maturation of foregut organs.

    abstract::The developmental stages of each foregut organ are intimately linked to the development of the other foregut organs such that the ultimate function of any one foregut organ, such as the metabolic function of the liver, depends on organizational changes associated with the maturation of multiple foregut organs. These c...

    journal_title:Pediatric research

    pub_type: 杂志文章,评审

    doi:10.1038/pr.2013.201

    authors: Arterbery AS,Bogue CW

    更新日期:2014-01-01 00:00:00

  • Growth trajectories of extremely low birth weight infants from birth to young adulthood: a longitudinal, population-based study.

    abstract::We compared sex-specific growth attainment of a population-based cohort of 147/166 (89%) extremely low birthweight (ELBW < 1000 g) and 131/145 (90%) sociodemographically comparable normal birthweight (NBW) cohort at young adulthood, and examined the pattern of growth trajectories and correlates of growth at ages 1, 2,...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.pdr.0000246201.93662.8e

    authors: Saigal S,Stoskopf B,Streiner D,Paneth N,Pinelli J,Boyle M

    更新日期:2006-12-01 00:00:00

  • Chronic neutropenia and defect in superoxide generation of granulocytes in two patients: enhancement of bactericidal capacity and respiratory burst activity by treatment with recombinant human granulocyte colony-stimulating factor.

    abstract::We have identified two unrelated girls with chronic neutropenia [absolute neutrophil counts (ANC) 10-870 and 10-940/microL in patients 1 and 2, respectively] and severe defect in superoxide anion generation by granulocytes. Formyl-methionyl-leucyl-phenylalanine-induced superoxide release was 1.2 +/- 0.9 and 1.9 +/- 1....

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199501000-00011

    authors: Káposzta R,Maródi L

    更新日期:1995-01-01 00:00:00

  • Developmental expression of vasoactive and growth factors in human lung. Role in pulmonary vascular resistance adaptation at birth.

    abstract::The factors that mediate the postnatal fall in pulmonary vascular resistance, which is crucial for normal gas exchange, are not fully understood. The endothelium has been implicated in this phenomenon, through the release of vasorelaxant factors such as nitric oxide (NO). Human pulmonary expression of endothelial NO s...

    journal_title:Pediatric research

    pub_type: 杂志文章,评审

    doi:10.1203/01.PDR.0000159575.58834.8D

    authors: Lévy M,Maurey C,Dinh-Xuan AT,Vouhé P,Israël-Biet D

    更新日期:2005-05-01 00:00:00

  • Creatine deficiency in the brain: a new, treatable inborn error of metabolism.

    abstract::In a patient with extrapyramidal movement disorder and extremely low creatinine concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy disclosed a generalized depletion of creatinine in the brain. Oral substitution of arginine, a substrate for creatine synthesis, resulted in an increase of b...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199409000-00023

    authors: Stöckler S,Holzbach U,Hanefeld F,Marquardt I,Helms G,Requart M,Hänicke W,Frahm J

    更新日期:1994-09-01 00:00:00

  • Novel red cell indices indicating reduced availability of iron are associated with high erythropoietin concentration and low ph level in the venous cord blood of newborns.

    abstract::There is evidence that an elevated erythropoietin (EPO) concentration is associated with signs of iron deficient erythropoiesis. The aim of this study was to evaluate the iron status by means of novel cellular indices and serum iron markers and to determine whether these are associated with EPO and pH in the venous co...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/PDR.0b013e318179957d

    authors: Ervasti M,Sankilampi U,Heinonen S,Punnonen K

    更新日期:2008-08-01 00:00:00

  • The adaptation of neonatal blood to metabolic acidosis and its effect on cisternal oxygen tension.

    abstract::In eight newborn lambs, the adaption of blood to acidosis was studied by sequential measurements of P50 in vitro (pH 7.4; 37 degrees C) and P50 in vivo (animal's pH and temperature, 39 degrees C) during the course of HCl-induced metabolic acidosis. The benefit of the change in both P50 on tissue oxygen tension was stu...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:

    authors: Berthiaume Y,Bureau MA,Bégin R

    更新日期:1981-05-01 00:00:00

  • Frequency, tidal volume, and mean airway pressure combinations that provide adequate gas exchange and low alveolar pressure during high frequency oscillatory ventilation in rabbits.

    abstract::We studied healthy and saline lavaged rabbits during high frequency oscillatory ventilation to determine what combination of frequency (f), tidal volume (Vt), and mean airway pressure (Paw) produced the lowest peak-to-peak alveolar pressure amplitude (Palv) and physiologic blood gas tensions. Sinusoidal volume changes...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199001000-00018

    authors: Kamitsuka MD,Boynton BR,Villanueva D,Vreeland PN,Frantz ID 3rd

    更新日期:1990-01-01 00:00:00

  • Recovery of treatment doses of surfactants from the lungs and vascular compartments of mechanically ventilated premature rabbits.

    abstract::Premature rabbits delivered by cesarean section at 28 d of gestation were each given intratracheally 75 mg/kg of radiolabeled preparation of either natural rabbit surfactant, natural calf surfactant, or surfactant-TA. Each newborn rabbit was ventilated for up to 6 h in a ventilator-plethysmograph with individual adjus...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198904000-00024

    authors: Seidner SR,Jobe AH,Ruffini L,Ikegami M,Pettenazzo A

    更新日期:1989-04-01 00:00:00

  • Transient partial hGH deficiency in prepubertal children with delay of growth.

    abstract:UNLABELLED:The hGH response to an ornithin or an insulin test was measured in 105 children from 11-18 yr old with delay of growth more than 2 SD. Besides 74 subjects with normal values and 7 with complete lack of response, 24 subjects exhibited a partial rise of GH. Most of the latter had decreasing growth rate and no ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197904000-00002

    authors: Gourmelen M,Pham-Huu-Trung MT,Girard F

    更新日期:1979-04-01 00:00:00

  • Gestational changes in renal responsiveness to cortisol in the ovine fetus.

    abstract::The ontogenetic renal responsiveness to exogenous cortisol was examined in the chronically cannulated ovine fetus. The contribution of effects at proximal and distal tubule of the kidney were studied also. Cortisol (81.5 micrograms/h) was infused into immature ovine fetuses (mean gestational age -113.9 days) on five o...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198907000-00002

    authors: Towstoless MK,McDougall JG,Wintour EM

    更新日期:1989-07-01 00:00:00

  • Endothelin A receptor blockade decreases pulmonary vascular resistance in premature lambs with hyaline membrane disease.

    abstract::Endothelin (ET)-1 is a potent vasoconstrictor peptide that modulates basal pulmonary vascular resistance (PVR) in the normal ovine fetus and contributes to high PVR after chronic intrauterine pulmonary hypertension. Although high PVR is present in premature lambs with severe hyaline membrane disease (HMD), whether ET-...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199808000-00006

    authors: Ivy DD,Parker TA,Kinsella JP,Abman SH

    更新日期:1998-08-01 00:00:00

  • Functional activity of class-specific antibodies to type III, group B streptococcus.

    abstract::The functional activity of naturally acquired IgG and IgM with specificity for the capsular polysaccharide of type III, group B Streptococcus (III-GBS) was compared. Sera collected during convalescence from 14 infants who had developed specific antibodies following III-GBS infection were employed for separation of IgG...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198801000-00007

    authors: Campbell JR,Baker CJ,Metzger TG,Edwards MS

    更新日期:1988-01-01 00:00:00