Genetic variant rs623011 (17q24.3) associates with non-familial thyrotoxic and sporadic hypokalemic paralysis.
BACKGROUND
A recent genome-wide association study of Thai patients with thyrotoxic periodic paralysis (TPP) identified a novel genetic variant rs623011 located in chromosome 17q24.3, which may potentially reduce the transcription of Kir2.1 and total Kir current.


OBJECTIVE
The aim of this study was to evaluate whether this genetic variant was present in Chinese patients with TPP and sporadic periodic paralysis (SPP), the second leading cause of non-familial hypokalemic periodic paralysis (hypoKPP) in Asia.


METHODS
Ninety patients with TPP, 61 SPP, and 100 age and sex-matched healthy subjects were performed. Genomic DNA was isolated from blood leukocytes and analysis of rs623011 was performed by polymerase chain reaction and direct sequencing.


RESULTS
Compared with normal control, the frequency of the risk allele A of rs623011 was significantly higher in both TPP and SPP patients (73.9% versus 53.5%, p=0.001; 82.0% versus 53.5%, p<0.001, respectively) with the Odds ratios (95% confidence interval) 2.426 (1.348-4.369) and 4.488 (2.265-8.891), respectively. The frequency of the A allele of rs623011 was similar between TPP and SPP.


CONCLUSIONS
TPP and SPP have the same susceptible gene variant rs623011 and may share the pathogenic mechanism of reduced Kir current in skeletal muscle independent of thyroid hormone.
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Pei-Yi
PY
Chu
Chih-Jen
CJ
Cheng
Min-Hua
MH
Tseng
Sung-Sen
SS
Yang
Hsiang-Cheng
HC
Chen
Shih-Hua
SH
Lin
D000328:Adult; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000097:blood / Q000235:genetics* / Q000652:urine; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000097:blood / Q000235:genetics* / Q000652:urine
C546860:KCNJ18 protein, human; D024661:Potassium Channels, Inwardly Rectifying