Bossini-Castillo Lara, Simeon Carmen P, Beretta Lorenzo, Broen Jasper, Vonk Madelon C, Callejas José Luis, Carreira Patricia, Rodríguez-Rodríguez Luis, García-Portales Rosa, González-Gay Miguel A, Castellví Ivan, Camps María Teresa, Tolosa Carlos, Vicente-Rabaneda Esther, Egurbide María Victoria, Schuerwegh Annemie J, Hesselstrand Roger, Lunardi Claudio, van Laar Jacob M, Shiels Paul, Herrick Ariane, Worthington Jane, Denton Christopher, Radstake Timothy R D J, Fonseca Carmen, Martin Javier
Arthritis Res Ther. 2012 Dec 27;14(6):R273. doi: 10.1186/ar4124.
Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort.
The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay.
Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients.
Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.
钾离子电压门控通道震颤相关亚家族成员5（KCNA5）与血管张力调节有关，在缺氧期间对其抑制会导致肺血管收缩。最近，有报道称KCNA5基因座与患有肺动脉高压（PAH）的系统性硬化症（SSc）患者存在保护性关联。因此，本研究的目的是在一个独立的多中心白种人SSc队列中重复这些发现。
本研究纳入了来自五个欧洲国家的2343例SSc病例（179例PAH阳性，经右心导管检查确诊）和2690例匹配的健康对照。使用TaqMan单核苷酸多态性（SNP）基因分型检测对Rs10744676进行基因分型。
对所选KCNA5基因变异的个体人群分析未显示与SSc或任何已定义的亚组（例如，局限性皮肤型SSc、弥漫性皮肤型SSc、抗着丝点自身抗体阳性和抗拓扑异构酶自身抗体阳性）有显著关联。此外，汇总分析未发现与该疾病或任何亚组存在关联的显著证据，甚至在PAH阳性组中也未发现。PAH阳性患者与PAH阴性患者的比较显示患者之间无显著差异。
我们的数据不支持KCNA5作为SSc易感性因素或作为SSc患者PAH发生的遗传标志物发挥重要作用。
