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首页> 外文期刊>Arthritis & Rheumatism >Association of a KCNA5 gene polymorphism with systemic sclerosis–associated pulmonary arterial hypertension in the European Caucasian population
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Association of a KCNA5 gene polymorphism with systemic sclerosis–associated pulmonary arterial hypertension in the European Caucasian population

机译:在欧洲白种人中,KCNA5基因多态性与系统性硬化相关的肺动脉高压的相关性

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ObjectivePulmonary arterial hypertension (PAH) has emerged as a leading cause of death in systemic sclerosis (SSc). The genetic basis of PAH has been unraveled in recent years, with a major role played by transforming growth factor β receptors; however, some other candidate genes have also been advocated, including potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5). We undertook this study to determine whether KCNA5 polymorphisms confer susceptibility to SSc and its vascular phenotype, including PAH.MethodsFour KCNA5 single-nucleotide polymorphisms (SNPs), rs10744676, rs1860420, rs3741930, and rs2284136, were genotyped in a discovery set of 638 SSc patients and 469 controls. In addition, rs10744676 was genotyped in an independent replication sample (938 SSc patients and 564 controls) and in a cohort of 168 patients with different PAH subtypes.ResultsThe KCNA5 rs10744676 variant was found to be associated with SSc in the discovery sample, with an odds ratio (OR) of 0.62 (95% confidence interval [95% CI] 0.48–0.79, adjusted P = 0.0003) in comparison with controls (C allele frequency 11.4% versus 17.2%). When subphenotypes were investigated, an association was found solely for PAH associated with SSc (OR 0.31 [95% CI 0.13–0.71], adjusted P = 0.04). The other KCNA5 SNPs tested were not associated with any SSc subset. The above association with PAH associated with SSc was replicated in the second set. In the combined population, rs10744676 was strongly associated with PAH associated with SSc in comparison with controls (OR 0.36 [95% CI 0.21–0.63], P = 0.0002). In the independent cohort of patients with PAH, after investigating PAH subtypes, only rs10744676 showed an association with PAH associated with SSc.ConclusionOur results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc.
机译:目的肺动脉高压(PAH)已成为系统性硬化症(SSc)死亡的主要原因。近年来,PAH的遗传基础尚未阐明,其主要作用在于转化生长因子β受体。然而,还提出了其他一些候选基因,包括钾电压门控通道,与振动器相关的亚家族,成员5(KCNA5)。我们进行了这项研究来确定KCNA5多态性是否赋予SSc敏感性及其血管表型,包括PAH。和469个控件。此外,在独立的复制样本(938名SSc患者和564名对照)以及168名具有不同PAH亚型的患者队列中对rs10744676进行了基因分型。与对照组的比率(OR)为0.62(95%置信区间[95%CI] 0.48-0.79,调整后的P = 0.0003)(C等位基因频率11.4%对17.2%)。当研究亚表型时,仅发现与SSc相关的PAH有相关性(OR 0.31 [95%CI 0.13–0.71],调整后的P = 0.04)。测试的其他KCNA5 SNP与任何SSc子集均不相关。在第二组中重复了上述与SSc相关的PAH的关联。与对照组相比,rs10744676与rs10744676与与SSc相关的PAH密切相关(OR 0.36 [95%CI 0.21-0.63],P = 0.0002)。在独立的PAH患者队列中,在研究PAH亚型后,只有rs10744676显示与与SSc相关的PAH相关。结论我们的结果为KCNA5 rs10744676变异与与SSc相关的PAH之间存在相关性提供了第一个证据。

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  • 来源
    《Arthritis & Rheumatism》 |2010年第10期|p.3093-3100|共8页
  • 作者单位

    Université Paris Descartes, INSERM U781, Hôpital Necker, and Hôpital Cochin, Paris, France;

    Université Paris Diderot, Hôpital Bichat Claude Bernard, and Assistance Publique Hôpitaux de Paris, Paris, France;

    UMR CNRS-8071, INRA-1152, Université d'Evry Val d'Essonne, Evry, France;

    Université Paris Descartes, INSERM U781, and Hôpital Necker, Paris, France;

    Charité University Hospital, Berlin, Germany;

    INSERM CIC3, Centre Hospitalier Universitaire Grenoble, Grenoble, France;

    University of Florence, Florence, Italy;

    University Medical Center, Freiburg, Germany;

    Université Paris-Sud, INSERM U999, Hôpital Antoine-Béclère, and Assistance Publique Hôpitaux de Paris, Clamart, France;

    Université Lille II, Lille, France;

    Spedali Civili, Brescia, Italy;

    INSERM U618, IFR 135, and Centre Hospitalier Universitaire Bretonneau, Tours, France;

    |University of Cologne, Cologne, Germany;

    University of Verona, Verona, Italy;

    Université Louis Pasteur and Hôpital Hautepierre, Strasbourg, France;

    Second University of Naples, Naples, Italy;

    Université Pierre et Marie Curie, Hôpital Saint-Antoine, and Assistance Publique Hôpitaux de Paris, Paris, France;

    Université Paris-Sud, INSERM U999, Hôpital Antoine-Béclère, and Assistance Publique Hôpitaux de Paris, Clamart, France;

    Université Paris Descartes, Hôpital Cochin, and Assistance Publique Hôpitaux de Paris, Paris, France;

    University Sapienza of Rome, Rome, Italy;

    Centre Hospitalier Universitaire Grenoble, Grenoble, France;

    Friedrich-Alexander-University Erlangen–Nuremberg, Erlangen, Germany;

    |Université Paris 6, Hôpital Pitié-Salpêtrière, and Assistance Publique Hôpitaux de Paris, Paris, France;

    University Giessen and Kerckhoff Clinic, Bad Nauheim, Germany;

    Centre Hospitalier Universitaire J. Minjoz, Besançon, France;

    Université Paris Descartes, Université Paris Diderot, Hôpital Cochin, Hôpital Bichat Claude Bernard, and Assistance Publique Hôpitaux de Paris, Paris, France;

    Université Paris Diderot, Hôpital Bichat Claude Bernard, and Assistance Publique Hôpitaux de Paris, Paris, France;

    Université Paris Descartes, Hôpital Cochin, Paris, France;

    Université Paris Descartes, INSERM U781, and Hôpital Necker, Paris, and Université Versailles Saint Quentin Yvelines, Hôpital Ambroise Paré, and Assistance Publique Hôpitaux de Paris, Boulogne, France;

    Université Paris Descartes, INSERM U781, Hôpital Necker, and Hôpital Cochin, Paris, France;

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