The clinical and genetic features in a cohort of mainland Chinese patients with thyrotoxic periodic paralysis.
The clinical and genetic features in a cohort of mainland Chinese patients with thyrotoxic periodic paralysis.
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中国大陆甲状腺毒性周期性麻痹患者队列的临床和遗传特征
DOI：
10.1186/s12883-015-0290-8
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发表时间：
2015-03-21
期刊：
影响因子：
2.6
通讯作者：
Hong D
中科院分区：
文献类型：
--
作者：
Li X;Yao S;Xiang Y;Zhang X;Wu X;Luo L;Huang H;Zhu M;Wan H;Hong D
甲状腺毒性周期性麻痹（thyrotoxicperiodicparalysis，TPP）是一种以甲状腺功能亢进（hyperthyroidism，甲亢）为表现的反复发作的低钾血症和肌无力为特征的危及生命的通道病。最近的研究结果表明，内向整流K+（Kir）通道的缺陷与一些TPP患者。这种关联不仅存在于高加索人群（主要是巴西人）中，也存在于新加坡人群中。然而，潜在的遗传风险因素，中国大陆患者，TPP的情况下，在世界上最大的一组，在很大程度上unexplored.MethodsSamples的DNA从127个人TPP和102甲亢男性对照自报为中国大陆从2011年1月至2014年1月从5个临床中心收集。直接测序TPP患者和对照组的KCNJ2基因、KCNJ18基因以及17q24.3位点的多态性（rs623011和rs312691）。结果中国大陆TPP患者KCNJ18基因突变率为3. 1%。KCNJ18基因突变患者较无突变患者的发作时间短，肌肉酸痛和无力复发率高。17q24.3的等位基因（rs623011和rs312691）在TPP患者中比对照组更常见，因此是TPP的重要危险因素（比值比11.94和10.57; 95% CI 5.93 - 24.05和5.48 - 20.40; P = 1.81 × 10 − 14和1.07 × 10 − 14）结论KCNJ18基因变异在中国大陆TPP患者中仅占很小比例。KCNJ18突变患者与无KCNJ18突变患者之间存在显著的临床差异。此外，rs623011和rs312691位点与中国大陆TPP患者显着相关，并强调Kir2.1通道是TPP的致病靶点。
BackgroundThyrotoxic periodic paralysis (TPP) is a life-threatening channelopathy manifesting as recurrent episodes of hypokalemia and muscle weakness in the presence of hyperthyroidism. Recent findings indicate defects of inward rectifying K+ (Kir) channels are associated with some TPP patients. The associations are not only found in Caucasian population (mainly Brazilian), but also in Singaporean population. However, potential genetic risk factors for mainland Chinese patients, the largest group of TPP cases in the world, have been largely unexplored.MethodsSamples of DNA from 127 individuals with TPP and 102 hyperthyroidism male controls self-reported as mainland Chinese were collected from 5 clinical centers from Jan 2011 to Jan 2014. TheKCNJ2gene,KCNJ18gene, as well as loci polymorphisms (rs623011and rs312691) at 17q24.3 were directly sequenced in TPP patients and controls. Clinical data were summarized from TPP participants for genotype/phenotype correlations.Results3.1% of TPP cases harboredKCNJ18gene mutations in mainland Chinese patients. Patients withKCNJ18mutation had shorter attack duration, higher prevalence of muscle soreness and weakness recurrence than patients withoutKCNJ18mutation. The alleles at 17q24.3 (rs623011and rs312691) were more common in patients with TPP than in controls, and therefore were significant risk factors for TPP (odds ratio, 11.94 and 10.57; 95% CI, 5.93-24.05 and 5.48-20.40; P = 1.81 × 10−14and 1.07 × 10−14respectively).ConclusionsThis study demonstrates that theKCNJ18variants are only responsible for a small proportion of TPP patients in mainland China. There are significant clinical differences between patients withKCNJ18mutations and patients withoutKCNJ18mutations. In addition, the rs623011and rs312691 loci are significantly associated with TPP patients in mainland China, and highlight the Kir2.1 channel as a causative target in TPP.
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DOI：
10.1093/bioinformatics/btq452
发表时间：
2010-10-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Yang TP;Beazley C;Montgomery SB;Dimas AS;Gutierrez-Arcelus M;Stranger BE;Deloukas P;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
13.6
作者：
Lin, Shih-Hua;Huang, Chou-Long
通讯作者：
Huang, Chou-Long
影响因子：
30.8
作者：
Cheung, Ching-Lung;Lau, Kam-Shing;Kung, Annie W. C.
通讯作者：
Kung, Annie W. C.
甲状腺毒性周期性麻痹：临床挑战。
影响因子：
2.1
作者：
Vijayakumar A;Ashwath G;Thimmappa D
通讯作者：
Thimmappa D