Contribution of Asian haplotype of KCNJ18 to susceptibility to and ethnic differences in thyrotoxic periodic paralysis

Context and Objectives: Thyrotoxic periodic paralysis (TPP) is an acute complication of thyrotoxicosis that can be lethal. TPP is relatively rare in Caucasians but often affects young males in East Asian populations. This study aimed to clarify the contribution of KCNJ18 to susceptibility to TPP in East Asian populations.
Participants and Methods: The study comprised 635 participants including 13 Japanese patients with TPP, 208 Japanese patients with Graves’ disease without TPP, and 414 healthy control subjects from the Japanese [n=208], Korean [n=111], and Caucasian populations [n=95]. DNA samples from 29 subjects (13 with TPP, 8 with Graves’ disease, and 8 controls) were sequenced for KCNJ18, and all subjects (n=635) were genotyped for six variants of KCNJ18 and a polymorphism of KCNJ2 (rs312691).
Results: Six single nucleotide variants (SNVs) with amino acid substitutions were identified by direct sequencing of KCNJ18. Among these, four SNVs comprised three haplotypes under strong ...