Genome-wide Association Study of Thyrotoxic Periodic Paralysis
Date Issued
2014
Date
2014
Author(s)
Chang, Chia-Ling
Abstract
Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that most often affects East Asian males. It is most commonly observed in Graves’ disease(GD) patients but may occur with any etiology of thyrotoxicosis. The typical presentations of TPP are muscle paralysis and a variable degree of hypokalemia. Patients usually seek medical attention at the emergency room because of acute muscle weakness. The attacks are often preceded by heavy carbohydrate-rich meal, alcohol abuse or strenuous exercise, varying from mild weakness to total paralysis with complete recovery within 72 hours.
The pathogenesis of TPP still remains unclear, but it is known to be associated with hypokelamia which is caused by a massive shift of potassium into the intracellular compartments. In 2010, KCNJ18 gene mutations which alter the function of an inwardly rectifying potassium channel named Kir2.6 were identified as a cause of TPP. These KCNJ18 mutations are highly prevalent in individuals with TPP in Caucasian populations but are not common in individuals from Asia. This suggests that additional genetic variants may also contribute to TPP susceptibility, especially in Asian populations. In 2012, genome-wide association studies(GWAS) of TPP in a Thai population and southern Chinese independently identified a susceptibility locus on chromosome 17q24.3 which might have functions on regulating the expression of another potassium channel gene named KCNJ2.
In this study, we performed GWAS with 53 male TPP patients and 153 male GD controls diagnosed at National Taiwan University Hospital and identified a susceptibility locus also at 17q24.3 (rs992072: P=3.18×10-7,odds ratio=3.8). Direct sequencing of the coding region of KCNJ2 and KCNJ18 genes in TPP patients found no obvious disease-causing variants. Our results were compatible with previous studies from Thai and southern Chinese populations. Further work is needed to characterize the 17q24.3 region and to delineate the functional significance of the variant(s) in TPP susceptibility.
Subjects
KCNJ18
KCNJ2
低血鉀
甲狀腺毒性週期性癱瘓
全基因體相關研究
Type
thesis
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