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Sökning: WFRF:(Stridh M.)

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  • Johannesson, M, et al. (författare)
  • A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: the NIH heterogeneous stock
  • 2009
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1088-9051. ; 19:1, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • The laboratory rat (Rattus norvegicus) is a key tool for the study of medicine and pharmacology for human health. A large database of phenotypes for integrated fields such as cardiovascular, neuroscience, and exercise physiology exists in the literature. However, the molecular characterization of the genetic loci that give rise to variation in these traits has proven to be difficult. Here we show how one obstacle to progress, the fine-mapping of quantitative trait loci (QTL), can be overcome by using an outbred population of rats. By use of a genetically heterogeneous stock of rats, we map a locus contributing to variation in a fear-related measure (two-way active avoidance in the shuttle box) to a region on chromosome 5 containing nine genes. By establishing a protocol measuring multiple phenotypes including immunology, neuroinflammation, and hematology, as well as cardiovascular, metabolic, and behavioral traits, we establish the rat HS as a new resource for the fine-mapping of QTLs contributing to variation in complex traits of biomedical relevance.
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  • Elkadeem, M. R., et al. (författare)
  • Agrivoltaic systems potentials in Sweden : A geospatial-assisted multi-criteria analysis
  • 2024
  • Ingår i: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 356
  • Tidskriftsartikel (refereegranskat)abstract
    • Agrivoltaic systems represent an intelligent solution combining electricity production from solar photovoltaic technology with agricultural production to avoid land use conflicts. Geographic Information System technologies can support the implementation and spread of agrivoltaic systems by identifying the most suitable areas using useful spatially explicit information concerning techno-agro-socio-economic criteria. In this study, we have developed a procedure to identify and classify suitable areas for agrivoltaic systems in Sweden. An Ordinal Priority Approach based multi-criteria decision-making algorithm is established to calculate the weights of the selected evaluation criteria through expert interviews. The land use data refers to the Corine Land Cover 2018 product. The results show that about 8.6% of the Swedish territory, approximately 38,485 km2, is suitable for installing agrivoltaic systems. Among this area, about 0.2% is classified as “excellent”, about 15% as “very good”, about 72% as “good”, about 13% as “moderate”, and about 0.1% as “poor”. Most “excellent”-classified areas are in Kalmar, Skåne, and Gotland. In contrast, most “very good” sites are in Skåne, Kalmar, and Östergötland. By deploying vertically mounted agrivoltaic systems with bifacial photovoltaic modules, the total potential installed capacity for “excellent” areas is about 2.5 GWp, while for areas classified “excellent” and “very good” is about 221 GWp. The total “excellent” areas can potentially supply about 2.4 TWh of electricity against the electricity consumption in 2021 of about 143 TWh. On the other hand, the land classified as “excellent” and “very good” could potentially provide about 207 TWh. The County of Västra Götaland shows the greatest potentials in terms of total potential electricity supply from agrivoltaic systems with about 227 TWh, followed by Skåne with a total potential of 206 TWh. 
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  • Gianfrancesco, MA, et al. (författare)
  • Genetic risk factors for pediatric-onset multiple sclerosis
  • 2018
  • Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 24:14, s. 1825-1834
  • Tidskriftsartikel (refereegranskat)abstract
    • Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset <18 years ( n = 569) and controls ( n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases ( n = 7588). Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10−16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10−16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.
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  • Kular, L, et al. (författare)
  • DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
  • 2018
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2397-
  • Tidskriftsartikel (refereegranskat)abstract
    • The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here, we find that DRB1*15:01 is hypomethylated and predominantly expressed in monocytes among carriers of DRB1*15:01. A differentially methylated region (DMR) encompassing HLA-DRB1 exon 2 is particularly affected and displays methylation-sensitive regulatory properties in vitro. Causal inference and Mendelian randomization provide evidence that HLA variants mediate risk for MS via changes in the HLA-DRB1 DMR that modify HLA-DRB1 expression. Meta-analysis of 14,259 cases and 171,347 controls confirms that these variants confer risk from DRB1*15:01 and also identifies a protective variant (rs9267649, p < 3.32 × 10−8, odds ratio = 0.86) after conditioning for all MS-associated variants in the region. rs9267649 is associated with increased DNA methylation at the HLA-DRB1 DMR and reduced expression of HLA-DRB1, suggesting a modulation of the DRB1*15:01 effect. Our integrative approach provides insights into the molecular mechanisms of MS susceptibility and suggests putative therapeutic strategies targeting a methylation-mediated regulation of the major risk gene.
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  • Forsberg, A., et al. (författare)
  • The Immune Response of the Human Brain to Abdominal Surgery
  • 2017
  • Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 81:4, s. 572-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [C-11]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [C-11]PBR28 binding of 26 +/- 26% (mean +/- standard deviation) at 3 to 4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 +/- 39%) on the 3rd to 4th postoperative day, corresponding to changes in [C-11]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [C-11]PBR28 binding (p=0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function.
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  • Platonov, Pyotr, et al. (författare)
  • Left atrial appendage activity translation in the standard 12-lead ECG
  • 2011
  • Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 22:6, s. 706-710
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract in UndeterminedLAA Activity in Surface ECG. Introduction: Interatrial frequency gradient is used to guide catheter ablation of atrial fibrillation (AF). Lead V1 adequately reflects right atrial activity, but reliable tools for noninvasive estimation of right versus left fibrillatory frequency are lacking. In this study, patients with dissociated left and right atrial rhythms were studied in order to identify which surface electrocardiographic (ECG) leads that most closely reflect the left atrial activity.Methods: Two consecutive patients with atrial tachycardia confined to the left atrial appendage (LAA) detected during catheter ablation of AF were included (2 men, 54 and 72 years old). A 12-lead ECG was recorded simultaneously with electrograms from the right and left atrial appendages (RAA/LAA). AF frequency spectra were calculated from all 12 leads using spatiotemporal QRST cancellation and Welch periodogram. The dominating atrial cycle length (DACL) in the surface ECG leads was subsequently compared with the invasively measured LAA cycle length.Results: LAA activation frequency was seen as a prominent peak in the frequency–power spectrum derived from frontal plane leads as well as lead V1. The absolute difference in noninvasively and invasively measured LAA cycle length was lowest for leads aVR, II, aVF, III, and V1 in which it was in the range of 2–4 ms.Conclusion: Prominent left atrial component is present in the majority of standard ECG leads, including those traditionally associated with right atrial activity such as V1. Spectral analysis is able to extract the LAA component on surface ECG.
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  • Stridh, Sara, et al. (författare)
  • Angiotensin converting enzyme inhibition blocks interstitial hyaluronan dissipation in the neonatal rat kidney via hyaluronan synthase 2 and hyaluronidase 1.
  • 2011
  • Ingår i: Matrix biology : journal of the International Society for Matrix Biology. - : Elsevier BV. - 1569-1802 .- 0945-053X. ; 30:1, s. 62-9
  • Tidskriftsartikel (refereegranskat)abstract
    • A functional renin-angiotensin system (RAS) is required for normal kidney development. Neonatal inhibition of the RAS in rats results in long-term pathological renal phenotype and causes hyaluronan (HA), which is involved in morphogenesis and inflammation, to accumulate. To elucidate the mechanisms, intrarenal HA content was followed during neonatal completion of nephrogenesis with or without angiotensin converting enzyme inhibition (ACEI) together with mRNA expression of hyaluronan synthases (HAS), hyaluronidases (Hyal), urinary hyaluronidase activity and cortical lymphatic vessels, which facilitate the drainage of HA from the tissue. In 6-8days old control rats cortical HA content was high and reduced by 93% on days 10-21, reaching adult low levels. Medullary HA content was high on days 6-8 and then reduced by 85% to 12-fold above cortical levels at day 21. In neonatally ACEI-treated rats the reduction in HA was abolished. Temporal expression of HAS2 corresponded with the reduction in HA content in the normal kidney. In ACEI-treated animals cortical HAS2 remained twice the expression of controls. Medullary Hyal1 increased in controls but decreased in ACEI-treated animals. Urine hyaluronidase activity decreased with time in control animals while in ACEI-treated animals it was initially 50% lower and did not change over time. Cells expressing the lymphatic endothelial mucoprotein podoplanin in ACEI-treated animals were increased 18-fold compared to controls suggesting compensation. In conclusion, the high renal HA content is rapidly reduced due to reduced HAS2 and increased Hyal1 mRNA expressions. Normal angiotensin II function is crucial for inducing these changes. Due to the extreme water-attracting and pro-inflammatory properties of HA, accumulation in the neonatally ACEI-treated kidneys may partly explain the pathological renal phenotype of the adult kidney, which include reduced urinary concentration ability and tubulointerstitial inflammation.
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  • Bollmann, A, et al. (författare)
  • Frequency measures obtained from the surface electrocardiogram in atrial fibrillation research and clinical decision-making
  • 2003
  • Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 14:s10, s. 154-161
  • Tidskriftsartikel (refereegranskat)abstract
    • Frequency Measures in AF. Introduction: Frequency analysis of fibrillation (FAF) and time-frequency analysis (TFA) were developed recently in order to quantify atrial electrical remodeling in atrial fibrillation (AF) from the surface ECG. This article describes the experience with these two different frequency analysis techniques in consecutive AF patients and discusses possible applications in AF research and clinical decision-making. Methods and Results: Baseline 2-minute, high-gain, high-resolution ECG recordings using three bipolar leads were obtained from 80 consecutive patients with AF lasting >24 hours. A power spectrum was obtained using Fourier analysis following spatiotemporal QRST cancellation. The dominant fibrillatory rate (in fibrillations per minute [fpm]) was derived (FAF). Stability of the instantaneous fibrillatory rate measured in overlapping 1-second segments was expressed as the segment proportion with consecutive rate differences <6 fpm (TFA). An adequate power spectrum that could be submitted for determination of fibrillatory rate was obtained in all patients. Dominant atrial rates ranged between 288 and 534 fpm and showed a high correlation (R = 0.878-0.911, P < 0.001) when assessed from the three different leads. The average instantaneous fibrillatory rate was inversely related with its stability (R = -0.417, P < 0.001). It was closely related with the dominant fibrillatory rate obtained from FAF (R = 0.948, P < 0.001). A literature review revealed that pharmacologic or electrical cardioversion and AF pace termination success rates were highly dependent on fibrillatory rate. Conclusion: Atrial fibrillatory rate and its variability can be reliable obtained from the surface ECG in AF patients. These parameters exhibit a significant interindividual variability allowing individual quantification of the atrial electrical remodeling process and might prove useful for predicting therapy efficacy.
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  • Bönlökke, J. H., et al. (författare)
  • Upper-airway inflammation in relation to dust spiked with aldehydes or glucan
  • 2006
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 32:5, s. 374-382
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Organic dust is associated with adverse effects on human airways. This study was done to investigate whether the addition of β-(1,3)-D glucan or aldehydes to office dust causes enhanced inflammation in human airways. Methods Thirty-six volunteers were exposed randomly to clean air, office dust, dust spiked with glucan, and dust spiked with aldehydes. The three dust exposures contained between 332 and 379 µg dust/m3. Spiking with 1 gram of dust was done with 10 milligrams of glucan or 0.1 microliters of aldehydes. Acoustic rhinometry, rhinostereometry, nasal lavage, and lung function tests were applied. Results After the exposures to dust spiked with the glucan and aldehydes, the nasal volume decreased (–1.33 and –1.39 cm3 (mean), respectively) when compared with the –0.9 cm3 after clean air or office dust (P=0.036 for a difference in decrease between exposures). After 2–3 hours the aldehyde-spiked dust caused a 0.6-mm swelling of the inferior turbinate, and glucan-spiked dust produced a 0.7-mm swelling (P=0.039 for a difference in the swelling between the four exposures). The preexposure nasal lavage cleaned off the mucosa, and lower cytokine concentrations were found after all of the exposures. For interleukin-8, this decrease in concentration was smaller after the dust exposures spiked with glucan and aldehydes (–2.9 and –25.8 pg/ml, respectively) than after office dust or clean air (–65.9 and –74.1 pg/ml, respectively) (P=0.042). The nasal eosinophil cell concentration increased after exposure to dust spiked with glucan (P=0.045). Conclusions β-(1,3)-D glucan and aldehydes in office dust enhance the inflammatory effects of dust on the upper airways
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  • Campana, Pietro Elia, 1984-, et al. (författare)
  • Experimental results, integrated model validation, and economic aspects of agrivoltaic systems at northern latitudes
  • 2024
  • Ingår i: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 437
  • Tidskriftsartikel (refereegranskat)abstract
    • Agrivoltaic systems, which allow the coexistence of crop and electricity production on the same land, are an integrated water–energy–food nexus solution that allows the simultaneous attainment of conflicting Sustainable Development Goals. This study aims to analyse experimental results on the responses of ley grass yield and quality to shadings in the first agrivoltaic system in Sweden. It also aims to validate an integrated modelling platform for assessing agrivoltaic systems' performances before installation. An economic analysis is carried out to compare the profitability of agrivoltaic versus conventional ground-mounted photovoltaic systems and, using a Monte Carlo Analysis, to identify the parameters that most affect the profitability. Despite the agrivoltaic systems’ supporting structures and photovoltaic modules producing an average ∼25% reduction in photosynthetically active radiation at ground level, no statistically significant difference was observed between the yield of the samples under the agrivoltaic system compared to the yield of the samples in the reference area. The agrivoltaic system attained land equivalent ratios of 1.27 and 1.39 in 2021 and 2022, respectively. The validation results of the integrated modelling platform show that the sub-model concerning the crop yield response to shading conditions tends to underestimate ∼7% the actual average crop yield under the agrivoltaic system. The results of the economic analysis show that, from a net present value perspective, agrivoltaic systems have a profitability that is ∼30 times higher than a conventional crop rotation in Sweden.
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  • Campana, Pietro Elia, 1984-, et al. (författare)
  • Optimisation of vertically mounted agrivoltaic systems
  • 2021
  • Ingår i: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 325
  • Tidskriftsartikel (refereegranskat)abstract
    • Agrivoltaic systems represent a key technology for reaching sustainable development goals, by reducing the competition of land used for food versus land used for electricity. Moreover, agrivoltaic systems are at the centre of the nexus between electricity production, crop production, and irrigation water savings. In this study, an optimisation model for vertically mounted agrivoltaic systems with bifacial photovoltaic modules is developed. The model combines three main sub-models: solar radiation and shadings, photovoltaics, and crop yield. Validation of the sub-models is performed showing good agreement with measured data and commercial software. The optimisation model is set as multi objective to explore the trade-offs between competing agrivoltaic key performance indicators. Oats and potatoes are used as reference crops in this study. The results show that the row distance between bifacial photovoltaic module structures significantly affects the photosynthetically active radiation distribution. The resulting crop yield of oats and potato is reduced by about 50% as row distance decreases from 20 m to 5 m. The implementation of an agrivoltaic system for the investigated crops at the chosen location shows a land equivalent ratio above 1.2, which justifies the use of the technology for reaching national sustainability goals.
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  • Eriksson, C., et al. (författare)
  • Golimumab är effektivt vid ulcerös kolit under svenska förhållanden. Interimsanalys av en svensk prospektiv multi-centerstudie, GO-SWIBREG
  • 2018
  • Konferensbidrag (refereegranskat)abstract
    • Bakgrund: Randomiserade kontrollerade prövningar har visat effekt av golimumab vid ulcerös kolit men studiedeltagare och förhållanden i kliniska prövningar motsvarar inte alltid svensk klinisk vardag. Syftet med denna studie var att utvärdera säkerhet och effekt av behandling med golimumab vid ulcerös kolit under svenska förhållanden.Metod: Detta är en prospektiv kohortstudie med inklusion av patienter från svenska sjukhus. Patienter med måttlig till svår aktiv ulcerös kolit, definierad som endoskopiskt Mayo score ≥2 och som påbörjade golimumab fr.o.m. 1/6-2014 inkluderades efter att informerat samtycke inhämtats. Kliniska karakteristika, behandling, klinisk-, biokemisk- och endoskopisk aktivitet liksom skattning av livskvalité samlades in vid inklusion samt prospektivt med hjälp av ett elektroniskt studieformulär, integrerat i svenska kvalitetsregistret för IBD (SWIBREG). Primärt effektmått var klinisk effekt vid 3 samt 12 månader (definierat som minskat Mayo score med ≥3 poäng eller 30 % från inklusion), samt klinisk remission (definierad som Mayo score ≤ 2 utan några enskilda poäng >1). Kontinuerliga data presenteras som median och kvartilavstånd. För statistisk jämförelse mellan inklusion och uppföljning användes Wilcoxon-signed rank test. Data från induktionsbehandling samt 3-månadersuppföljning presenteras här.Resultat: 50 patienter inkluderades t.o.m. 15/9-2017. Vid studiestart var 24/50 (48 %) samtidigt behandlade med immunmodulerare, 16/50 (32 %) med perorala kortikosteroider samt 27/50 (54 %) med 5-ASA. Totalt hade 35/50 (70 %) tidigare fått behandling med minst en TNF-hämmare (tabell 1). Efter 12 veckor hade 37/50 (74 %), fortfarande behandling med golimumab. Av de patienter som fortsatte med golimumab till vecka 12 var 8 (22 %) i klinisk remission och 13 (35 %) uppvisade klinisk respons. Totalt Mayo score minskade i median från 7 (6-10) vid inklusion till 5 (1-8) vid 12 veckor (p<0.01). Fekalt calprotektin minskade från 710 (275-1850) µg/g till 390 (45-870) µg/g (p=0.02). Livskvalitet hos golimumab-behandlade patienter förbättrades, uppmätt som en signifikant minskning av poäng på short health scale (p=0.04).Slutsats: Golimumab-behandlade patienter i Sverige utgör en svårbehandlad grupp. Trots det kan förbättring av kliniska parametrar, inflammatorisk aktivitet och upplevd livskvalité uppnås redan efter 12 veckors golimumab-behandling.
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  • Husser, Daniela, et al. (författare)
  • A Genotype-Dependent Intermediate ECG Phenotype in Patients With Persistent Lone Atrial Fibrillation Genotype ECG-Phenotype Correlation in Atrial Fibrillation
  • 2009
  • Ingår i: Circulation: Arrhythmia and Electrophysiology. - 1941-3149 .- 1941-3084. ; 2:1, s. 24-28
  • Konferensbidrag (refereegranskat)abstract
    • Background-Atrial fibrillation (AF) is heterogeneous at the clinical and molecular levels. Association studies have reported that common single-nucleotide polymorphisms in KCNE1 and SCN5A may predispose to AF In this study, we tested the hypothesis that specific AF-associated genotypes confer variation on the appearance of AF assessed by analysis of fibrillatory rate of the atria. Methods and Results-Twenty-six nonrelated patients (21 males, mean age 55 +/- 12 years) with persistent lone AF (median AF duration 5 weeks) not taking class I or III antiarrhythmic drugs were studied. Fibrillatory rate was obtained by spatiotemporal QRST cancellation and time-frequency analysis of the index surface ECG. Genotypes at the AF-associated loci in KCNE1 (S38G) and SCN5A (H558R) were determined by direct DNA sequencing. The atrial fibrillatory rate was 418 +/- 50 fibrillations per minute (range, 336 to 521) in the study cohort. Carriers of the 38 GG KCNE1 genotype (n=13) had significantly lower fibrillatory rates (392 +/- 36 versus 443 +/- 49 fibrillations per minute, P=0.006) compared to those with GS or SS genotype (n=13). Six patients (23%) with fibrillatory rates >450 fibrillations per minute, all had either the GS or SS genotype (chi(2) P=0.008). In contrast, both the heterozygeous and homozygeous SCN5A H558R polymorphism had no effect on fibrillatory rate. There were no significant associations between fibrillatory rate and clinical (age, gender, AF duration, drug treatment) or echocardiographic (left atrial diameter, left ventricular ejection fraction) variables. In multivariable regression analysis, the KCNE1 S38G genotype (SS/GS coded 0, GG coded 1) was the only independent predictor of fibrillatory rate (beta = -0.437, P=0.006) with a SE of the estimate of 44 fibrillations per minute. Conclusions-This study suggests that atrial fibrillatory rate obtained from the surface ECG is at least in part determined by KCNE1 (S38G) genotype, implying that this variant exerts functional effects on atrial electrophysiology. This intermediate ECG phenotype may be useful for elaborating genetic influences on AF mechanisms and identifying subsets of patients for variability in AF susceptibility or response to therapies. (Circ Arrhythmia Electrophysiol. 2009;2:24-28.)
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