Association of novel single nucleotide polymorphisms in the calcium channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic paralysis

Thyrotoxic (hypokalemic) periodic paralysis (TPP) is a frequent complication of thyrotoxicosis among Chinese men. To determine the genetic association of TPP, we studied 97 male TPP patients, 77 Graves' disease patients without TPP, and 100 normal male subjects. Mutations of the voltage-depende...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2004-03, Vol.89 (3), p.1340-1345
Main Authors: Kung, Annie W C, Lau, K S, Fong, G C Y, Chan, Vivian
Format: Article
Language:English
Subjects:
5' Flanking Region - genetics
Adult
Calcium Channels - genetics
Chromosomes, Human, Pair 1
Genotype
Humans
Male
Microsatellite Repeats
Middle Aged
Muscle Proteins - genetics
NAV1.4 Voltage-Gated Sodium Channel
Paralyses, Familial Periodic - genetics
Polymorphism, Single Nucleotide
Potassium Channels - genetics
Potassium Channels, Voltage-Gated
Shaw Potassium Channels
Sodium Channels - genetics
Thyrotoxicosis - genetics
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Summary:Thyrotoxic (hypokalemic) periodic paralysis (TPP) is a frequent complication of thyrotoxicosis among Chinese men. To determine the genetic association of TPP, we studied 97 male TPP patients, 77 Graves' disease patients without TPP, and 100 normal male subjects. Mutations of the voltage-dependent calcium channel (Ca(v)1.1), sodium channel (Na(v)1.4), and potassium channel (K(v)3.4), and association of the microsatellite markers on chromosome 1 in the region of the Na/K-ATPase subunits alpha1, alpha2, and beta1 were studied. None of the TPP patients carried the known mutations in Ca(v)1.1, Na(v)1.4, and K(v)3.4 genes. There was no association of TPP with the microsatellite markers that mapped to 1p13, 1q21-23, and 1q22-25. We detected 12 single nucleotide polymorphisms (SNPs) in Ca(v)1.1 in our population, of which three were novel. Significant differences in the SNP genotype distribution between TPP compared with Graves' disease controls and normal controls were seen at the 5' flanking region nucleotide (nt) -476 (P = 0.02), intron 2 nt 57 (P < 0.01), and intron 26 nt 67 (P < 0.001). Because these SNPs lie at or near the thyroid hormone responsive element, it is possible that they may affect the binding affinity of the thyroid hormone responsive element and modulate the stimulation of thyroid hormone on the Ca(v)1.1 gene.
ISSN:0021-972X
DOI:10.1210/jc.2003-030924