Thyrotoxic Periodic Paralysis and Polymorphisms of the ADRB2, AR, and GABRA3 Genes in Men with Graves Disease

Abstract

BackgroundThyrotoxic periodic paralysis (TPP) is a rare complication of thyrotoxicosis characterized by acute attacks of muscle weakness and hypokalemia. Recently, variation in several genes was suggested to be associated with TPP. This study evaluated the genetic predisposition to TPP in terms of the β2-adrenergic receptor (ADRB2), androgen receptor (AR), and γ-aminobutyric acid receptor α3 subunit (GABRA3) genes.MethodsThis study enrolled 48 men with Graves disease (GD) and TPP, and 48 GD patients without TPP. We compared the frequencies of candidate polymorphisms between the two groups.ResultsThe frequency of the Gly16/Gly16 genotype in ADRB2 was not significantly associated with TPP (P=0.32). More CAG repeats (≥26) in the AR gene were not correlated with TPP (odds ratio [OR], 2.46; 95% confidence interval [CI], 0.81 to 8.09; P=0.08). The allele frequency of the TT genotype in the GABRA3 gene was not associated with TPP (OR, 1.83; 95% CI, 0.54 to 6.74; P=0.41).ConclusionThe polymorphisms in the ADRB2, AR, and GABRA3 genes could not explain the genetic susceptibility to TPP in Korean men with GD.

Association of KCNJ2 Genetic Variants with Susceptibility to Thyrotoxic Periodic Paralysis in Patients with Graves’ Disease

“…The hyperthyroid state may confer a genetic predilection to abnormal electrical potential in muscles, leading to accelerated intracellular shifts of potassium [23]. To define the genetic susceptibility to TPP, we previously evaluated several genes that are associated with androgen receptors and adrenergic receptors [14]. However, we could not demonstrate any significant associations with TPP.…”

“…43 male GD patients with TPP were recruited and 40 male GD patients without TPP were recruited as controls between 2001 and 2006 at Asan Medical Center, Seoul, Korea. GD was diagnosed on the basis of the presence of a diffuse goiter, positivity for one or more anti-thyroid antibodies, suppressed serum TSH levels, and increased serum free T4 levels, as previously described [14]. Patients with TPP displayed acute muscle weakness and hypokalemia in a thyrotoxic state.…”

RNASET2,GPR174, and PTPN22 gene polymorphisms are related to the risk of liver damage associated with the hyperthyroidism in patients with Graves’ disease

“…GD is an autoimmune disorder where autoantibodies target antigens expressed in thyroid tissues and hence hyperthyroidism is promoted. 14,19,20 Consensus has been reached that several genetic and environmental factors would affect GD. 2,14 On the other hand, there has been evidence suggesting that part of untreated GD patients tend to suffer from LD.…”

Articles inEndocrinology and Metabolismin 2016

“…RAI therapy and low initial titers of thyroglobulin (Tg) and anti-Tg antibody were significant protective factors against disease recurrence among low-risk PTC patients. Park et al [4] evaluated the genetic predisposition to thyrotoxic periodic paralysis (TPP) in terms of the β2-adrenergic receptor, androgen receptor, and γ-aminobutyric acid receptor α3 subunit genes and found no associations of these polymorphisms with TPP. In another article, doctors from the University of the Philippines also reported that fixed-dose radioiodine was associated with a significantly lower incidence of persistent hyperthyroidism at 6 months after radioactive therapy for the treatment of Graves disease [5].…”