HLA and Thyrotoxic Periodic Paralysis in Japanese Patients

Abstract

Periodic paralysis (PP) is a well recognized although rare and peculiar complication of thyrotoxicosis, especially among Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked to certain immunogenetic factors, and increased frequency of certain HLA antigens has been found in patients with Graves' disease. This study was, therefore, undertaken to determine HLA haplotypes in Japanese men with thyrotoxic periodic paralysis (TPP). HLA typing in 35 TPP patients and 263 normal men and women demonstrated highly significant increases (P less than 0.01) in HLA-A2, Cw3, and DRw8 in the TPP patients. In comparing TPP patients with thyrotoxic men who did not have PP, the frequency of DRw8 antigen was 2.5-fold greater in patients with PP than in those without it (62.8% vs. 28.6%). The data suggest that the HLA-DRw8 gene itself may play a significant role in the susceptibility to TPP among Japanese men.

Thyrotoxic periodic paralysis as the first manifestation of a thyrotropin-secreting pituitary adenoma

“…Specifically, in patients with TPP a higher incidence of HLA B46, DR9 and DQB1 * 0303 has been documented in Hong Kong Chinese patients and HLA A2, BW22, AW19, B17 and DRW8 in Singapore Chinese and Japanese patients. [26][27][28] Moreover, an association between certain single-nucleotide polymorphisms (SNPs) of the L-type calcium channels a1-subunit Cav1.1 has been reported in Southern Chinese TPP patients. 29 However, no specific association of HLA haplotypes or SNPs polymorphisms and predisposition to TPP has been documented.…”

Comparison of the Incidence of Association of Periodic Paralysis and Hyperthyroidism in Japan in 1957 and 1991.

“…One of the reasons for this high incidence is genetic predisposition. HLA analysis of patients with thyrotoxic periodic paralysis carried out by Tamai et al [4] revealed that DRw8 is commonly associated with this abnormality in Japanese populations, while the study by Yeo [5] and Sum [6] revealed the importance of Bw22 as a genetic marker for Chinese thyrotoxic periodic paralysis patients.…”

Autonomously Functioning Thyroid Nodule Associated with Thyrotoxic Periodic Paralysis

“…The reason for the difference remains undefined. Previous studies suggest an association of genetic factors such as certain human leukocyte antigen haplotypes with TPP [15,16]. Interestingly TPP predominantly affects males despite the predominance of thyrotoxicosis in females.…”

“…Thus, the pathogenic role of ion channel defects in TPP remains under debate. Some studies suggested an association of certain human leukocyte antigen haplotypes with TPP [15,16].…”