Genetic variant rs623011 (17q24.3) associates with non-familial thyrotoxic and sporadic hypokalemic paralysis

Clin Chim Acta. 2012 Dec 24:414:105-8. doi: 10.1016/j.cca.2012.08.004. Epub 2012 Aug 15.

Abstract

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.

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Variation / genetics*
  • Humans
  • Hypokalemic Periodic Paralysis / blood
  • Hypokalemic Periodic Paralysis / genetics*
  • Hypokalemic Periodic Paralysis / urine
  • Male
  • Mutation
  • Polymerase Chain Reaction
  • Potassium Channels, Inwardly Rectifying / blood
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Potassium Channels, Inwardly Rectifying / urine

Substances

  • KCNJ18 protein, human
  • Potassium Channels, Inwardly Rectifying