The Study Of Single Nucleotide Polymorphisms Of L-type Votage-gated Calcium Channel α1 Subunit Gene (CACNA1S) 11 Exon In Thyrotoxic Periodic Paralysis Patients Of Chinese

Background: Thyrotoxic hypokalemic periodic paralysis(THPP) is a frequent complication of male thyrotoxicosis among Chinese.The pathogenesis of THPP remains unclear.There were some reports about that 3 SNPs(1491C→, T,1551T→, C,1564C→, T) of L-type votage-gated calcium channelα1 subunit gene (CACNA1S) 11 exon were detected in THPP patients.Objective: To investigate the single nucleotide polymorphisms (SNPs) of CACNA1S gene 11 exon in patients of thyrotoxic hypokalemic periodic paralysis(THPP),hypokalemic periodic paralysis(HPP) without hyperthyroidism, Graves' Disease(GD) without hypokalemic periodic paralysis and normal subjects in Chinese population in Sichuan area.Methods:The single nucleotide polymorphisms of CACNA1S gene 11 exon were analyzed in 22 sporadic THPP male patients, 23 HPP male patients(include 3 patients of renal tubule acidosis, 2 patients of primary aldosteronism, 1 patient of Gitelman syndrome, 2 patients of pheochromocytoma, 1 FHPP patients and 14 HPP patients with unclear cause), 33 GD male patients without hypokalemic periodic paralysis and 22 male normal subjects.Genomic DNA was prepared from the venous blood of all subjects.The target fragment was amplificated by polymerase chain reaction ,and then analyzed by direct DNA sequencing.The thyroid hormones include FT₄,FT₃ and TSH were measured in all subjects and potassium were measured in patients of THPP and HPP during attack.Results: 3 single nucleotide polymorphisms (SNPs) were detected among the 100 subjects (THPP patients,HPP patients,Graves' diease patients and normal subjects). Genotype(CT+TT) frequencies of 1491 C→, T were 45% (THPP), 30%( HPP),30%(GD), 27%(normal subjects) respectively.The genotype frequency of CT plus TT increased in THPP, but the association analysis in the four groups had no difference between each other(P=0.563). Frequencies of allele T were 25%(THPP), 15%(HPP), 15%(GD), 16%(normal subjects) respectively. The allelic frequency in THPP was higher than other three groups,but there was no significant difference between the four groups(P=0.530). Genotype(TC+CC) frequencies of 1551 C→, T were 50% (THPP), 39%(HPP), 33%(GD), 32%(normal subjects) respectively.Although the genotype frequency of TC plus CC increased in THPP, there was no significant difference between the four groups(P =0.568). Frequencies of allele C were 27%(THPP),22%(HPP),17%(GD), 18%( normal subjects).Also, The allelic frequency in THPP was higher than other three groups,.There was no significant difference(P=0.568). Genotype(CT) frequencies of 1564 C→, T were 5% (THPP), 9%(HPP), 6%(GD), 5%(normal subjects). Frequencies of allele T were 2%(THPP),4%(HPP), 2%(GD), 2%( normal subjects).The mutation frequency was too little to collect statistics.Conclusion: 3 single nucleotide polymorphisms of CACNA1S gene 11 exon definitely existed among the patients of THPP, HPP, Graves' Diease, and normal subjects,but there was no significant difference between the four groups about the genotype frequency and allelic frequency. But this study found there was a tendency exsiting in the results of statistics.In THPP patients ,genotype(CT+TT) frequency and frequency of allele T of 1491C→T were higher than other groups. Also in THPP patients ,genotype(TC+CC) frequency and frequency of allele C of 1551T→C were higher than other groups.Thus, these SNPs can't be determined to be the gene defect of THPP or not.