Genetic mapping for thyrotoxic periodic paralysis

Abstract

TPP is a complication of thyrotoxicosis affecting 25% of thyrotoxic southern Chinese male but not female patients. Paralysis due to hypokalemia typically occurs after a high carbohydrate meal. This episodic paralysis will remit with the control of thyrotoxicosis but may recur with relapse of the disease. Shifting of potassium into intracellular space results in hypokalemia and paralysis. Increased Na, K-ATPase activity has been observed in TPP patients when compared to thyrotoxic Graves’ disease (GD) patients and normal controls. To study the association of Na, K-ATPase genotype with TPP, we evaluated TPP patients (n = 100) and compared them to male GD patients without TPP (n = 60) and normal male subjects (n = 70). A set of polymorphic microsatellite markers with a genetic distance < 10 cM was used to study the allelic distribution. Our results showed that there was no significant difference between the 3 groups in the allelic distribution for all markers associated with the Na, K-ATPase α1 (1p13), α2 (1q21-23), α3 (19q13.2) and β1 (1q22-25), β2 (17p13.1), β3 (3q22-23) genes. There was also no association of CACNL1A3 (dihydropyridine sensitive calcium channel receptor gene, located at chromosome 1q32) with TPP. Mutation of CACNL1A3 gene is linked to Familial Hypokalemia Periodic Paralysis in Caucasians. On screening the X-chromosome, one of the alleles (size 289) of the marker DXS1214 in the region of Xp11.3-21 was observed to be more frequent in TPP subjects when compared to GD patients and normal subjects (p < 0.05), suggesting that this locus may be linked to TPP.