Thyrotoxic Periodic Paralysis, Susceptibility To, 3

For a general phenotypic description and a discussion of genetic heterogeneity of susceptibility to thyrotoxic periodic paralysis, see 188580.

Mapping

Cheung et al. (2012) conducted a genomewide association study and a replication study with a total of 123 southern Chinese with thyrotoxic periodic paralysis (TTPP) (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (600681) (rs312691; odds ratio = 3.3; p metaanalysis = 1.8 x 10(-14)). All subjects with TTPP also had Graves disease (275000), and subsequent TTPP versus Graves disease comparison confirmed that the association at 17q24.3 was specific to TTPP. The area under the curve of rs312691 genotype for risk prediction of TTPP in subjects with Graves disease was 0.73. Expression quantitative trait locus analysis identified SNPs in the region flanking rs312691 (+/- 10 kb) that could potentially affect KCNJ2 expression (p = 0.0001). The SNP rs312691 is located in a gene-poor region and is approximately 150 kb downstream of KCNJ2 and approximately 195 kb downstream of KCNJ16 (605722). Cheung et al. (2012) considered the KCNJ2 the more biologically plausible candidate gene for TTPP, as KCNJ16 is not expressed in skeletal muscle and KCNJ16 knockout mice have no behavioral or physical abnormalities.