Association study in Mexican patients with thyrotoxic hypokalemic periodic paralysis

Bautista‑Medina,Mario Arturo; Gallardo‑Blanco,Hugo Leonid; Martinez‑Garza,Laura Elia; Cerda‑Flores,Ricardo Martin; Lavalle‑Gonzalez,Fernando Javier; Villarreal‑Perez,Jesus Zacarias

doi:10.3892/br.2020.1331

Association study in Mexican patients with thyrotoxic hypokalemic periodic paralysis

Authors:
- Mario Arturo Bautista‑Medina
- Hugo Leonid Gallardo‑Blanco
- Laura Elia Martinez‑Garza
- Ricardo Martin Cerda‑Flores
- Fernando Javier Lavalle‑Gonzalez
- Jesus Zacarias Villarreal‑Perez
View Affiliations

Affiliations: Endocrinology Department, University Hospital José Eleuterio González, Autonomous University of Nuevo León, Monterrey, Nuevo León 64460, Mexico, Department of Genetics, University Hospital José Eleuterio González, Autonomous University of Nuevo León, Monterrey, Nuevo León 64460, Mexico, School of Nursing, Autonomous University of Nuevo León, Monterrey, Nuevo León 64460, Mexico
Published online on: July 17, 2020 https://doi.org/10.3892/br.2020.1331
Article Number: 24
Copyright: © Bautista‑Medina et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hypokalemic periodic paralysis type 1 (OMIM; HOKPP1) and type 2 (OMIM; HOKPP2) are diseases of the muscle characterized by episodes of painless muscle weakness, and is associated with low potassium blood levels. Hyperthyroidism has been associated with thyrotoxic periodic paralysis (TTPP) (OMIM; TTPP1 and TTPP2), and genetic susceptibility has been implicated. In the present study, the clinical and epidemiological characteristics of patients with TTPP are described, together with their association with genetic variants reported previously in other populations. A prospective and a retrospective search of the medical records of patients who attended the emergency department at the Hospital Universitario ‘Dr. Jose E. Gonzalez’ in Monterrey, Nuevo León, Mexico, and were diagnosed with TTPP was performed. A total of 16 gene variants in the genes MUC1, CACNA1S, KCNE3 and SCN4A, and nine ancestry informative markers (AIMs), were analysed by Multiplex TaqMan™ Open Array assay, and a genetic association study was performed. A total of 11 patients were recruited, comprising nine males and two females (age range, 19‑52 years) and 64 control subjects. Only two cases (18%) had a previous diagnosis of hyperthyroidism; the rest were diagnosed subsequently with Graves' disease. Based on the analysis, two DNA variants were found to potentially confer an increased risk for TTPP: S1PR1 rs3737576 [odds ratio (OR), 4.38; 95% confidence interval (CI), 1.08‑17.76] and AIM rs2330442 (OR, 4.50; 95% CI, 1.21‑16.69), and one variant was suggested to be possibly associated with TTPP, namely MUC1 rs4072037 (OR, 3.08; 95% CI, 0.841‑1.38). However, there were no statistically significant associations between any of the 24 DNA variants and TTPP in a population from northeast Mexico.

View Figures

View References

1	Amberger JS, Bocchini CA, Scott AF and Hamosh A: OMIM.org: Leveraging knowledge across phenotype-gene relationships. Nucleic Res. 47:D1038–D1043. 2019.PubMed/NCBI View Article : Google Scholar
2	Balakrishnan RK, Chandran SR, Thirumalnesan G and Doraisamy N: Thyrotoxic periodic paralysis. Indian J Endocrinol Metabolism. 15 (Suppl 2):S147–S149. 2011.PubMed/NCBI View Article : Google Scholar
3	Schalin-Jantti C, Laine T, Valli-Jaakola K, Lonnqvist T, Kontula K and Valimaki MJ: Manifestation, management and molecular analysis of candidate genes in two rare cases of thyrotoxic hypokalemic periodic paralysis. Horm Res. 63:139–144. 2005.PubMed/NCBI View Article : Google Scholar
4	Kung AW: Clinical review: Thyrotoxic periodic paralysis: A diagnostic challenge. J Clin Endocrinol Metab. 91:2490–2495. 2006.PubMed/NCBI View Article : Google Scholar
5	Tran HA: Inadvertent iodine excess causing thyrotoxic hypokalemic periodic paralysis. Arch Intern Med. 165:2536. 2005.PubMed/NCBI View Article : Google Scholar
6	Dias Da Silva MR, Cerutti JM, Arnaldi LA and Maciel RM: A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. J Clin Endocrinol Metab. 87:4881–4884. 2002.PubMed/NCBI View Article : Google Scholar
7	Kim TY, Song JY, Kim WB and Shong YK: Arg16Gly polymorphism in beta2-adrenergic receptor gene is not associated with thyrotoxic periodic paralysis in Korean male patients with Graves' disease. Clin Endocrinol (Oxf). 62:585–589. 2005.PubMed/NCBI View Article : Google Scholar
8	Kung AW, Lau KS, Cheung WM and Chan V: Thyrotoxic periodic paralysis and polymorphisms of sodium-potassium ATPase genes. Clin Endocrinol (Oxf). 64:158–161. 2006.PubMed/NCBI View Article : Google Scholar
9	Wang W, Jiang L, Ye L, Zhu N, Su T, Guan L, Li X and Ning G: Mutation screening in Chinese hypokalemic periodic paralysis patients. Mol Genet Metab. 87:359–363. 2006.PubMed/NCBI View Article : Google Scholar
10	Ryan DP, da Silva MR, Soong TW, Fontaine B, Donaldson MR, Kung AW, Jongjaroenprasert W, Liang MC, Khoo DH, Cheah JS, et al: Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. Cell. 140:88–98. 2010.PubMed/NCBI View Article : Google Scholar
11	Villarreal-Martinez A, Gallardo-Blanco H, Cerda-Flores R, Torres-Muñoz I, Gómez-Flores M, Salas-Alanís J, Ocampo-Candiani J and Martínez-Garza L: Candidate gene polymorphisms and risk of psoriasis: A pilot study. Exp Ther Med. 11:1217–1222. 2016.PubMed/NCBI View Article : Google Scholar
12	Gallardo-Blanco HL, Villarreal-Perez JZ, Cerda-Flores RM, Figueroa A, Sanchez-Dominguez CN, Gutierrez-Valverde JM, Torres-Muñoz IC, Lavalle-Gonzalez FJ, Gallegos-Cabriales EC and Martinez-Garza LE: Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study. Exp Ther Med. 13:523–529. 2017.PubMed/NCBI View Article : Google Scholar
13	Carpenter D, Ringrose C, Leo V, Morris A, Robinson RL, Halsall PJ, Hopkins PM and Shaw MA: The role of CACNA1S in predisposition to malignant hyperthermia. BMC Med Genet. 10(104)2009.PubMed/NCBI View Article : Google Scholar
14	Kung AW, Lau KS, Fong GC and Chan V: Association of novel single nucleotide polymorphisms in the calcium channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic paralysis. J Clin Endocrinol Metab. 89:1340–1345. 2004.PubMed/NCBI View Article : Google Scholar
15	Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 17:405–424. 2015.PubMed/NCBI View Article : Google Scholar
16	Kosoy R, Nassir R, Tian C, White PA, Butler LM, Silva G, Kittles R, Alarcon-Riquelme ME, Gregersen PK, Belmont JW, et al: Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America. Hum Mutat. 30:69–78. 2009.PubMed/NCBI View Article : Google Scholar
17	Kwon H, Jung JH, Han KD, Park YG, Cho JH, Lee DY, Han JM, Park SE, Rhee EJ and Lee WY: Prevalence and annual incidence of thyroid disease in Korea from 2006 to 2015: A nationwide population-based cohort study. Endocrinol Metab (Seoul). 33:260–267. 2018.PubMed/NCBI View Article : Google Scholar
18	Lu KC, Hsu YJ, Chiu JS, Hsu YD and Lin SH: Effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis. Am J Emerg Med. 22:544–547. 2004.PubMed/NCBI View Article : Google Scholar
19	Dias da Silva MR, Cerutti JM, Tengan CH, Furuzawa GK, Vieira TC, Gabbai AA and Maciel RM: Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha1 subunit gene (Cav1.1) are not associated with thyrotoxic hypokalaemic periodic paralysis. Clin Endocrinol(Oxf). 56:367–375. 2002.PubMed/NCBI View Article : Google Scholar
20	Nie M, Bal MS, Yang Z, Liu J, Rivera C, Wenzel A, Beck BB, Sakhaee K, Marciano DK and Wolf MT: Mucin-1 increases renal trpv5 activity in vitro, and urinary level associates with calcium nephrolithiasis in patients. J Am Soc Nephrol. 27:3447–3458. 2016.PubMed/NCBI View Article : Google Scholar
21	Meyer TE, Verwoert GC, Hwang SJ, Glazer NL, Smith AV, van Rooij FJ, Ehret GB, Boerwinkle E, Felix JF, Yang Q, et al: Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels. PLoS Genet. 6(e1001045)2010.PubMed/NCBI View Article : Google Scholar
22	Tin A, Kottgen A, Folsom AR, Maruthur NM, Tajuddin SM, Nalls MA, Evans MK, Zonderman AB, Friedrich CA, Boerwinkle E, et al: Genetic loci for serum magnesium among African-Americans and gene-environment interaction at MUC1 and TRPM6 in European-Americans: The Atherosclerosis Risk in Communities (ARIC) study. BMC Genet. 16(56)2015.PubMed/NCBI View Article : Google Scholar
23	Blaine J, Chonchol M and Levi M: Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. 10:1257–1272. 2015.PubMed/NCBI View Article : Google Scholar
24	Kardalas E, Paschou SA, Anagnostis P, Muscogiuri G, Siasos G and Vryonidou A: Hypokalemia: A clinical update. Endocr Connect. 7:R135–R146. 2018.PubMed/NCBI View Article : Google Scholar
25	1000 Genomes Project Consortium. Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA and Abecasis GR: A global reference for human genetic variation. Nature. 526:68–74. 2015.PubMed/NCBI View Article : Google Scholar
26	Wang W, Wang A, Luo G, Ma F, Wei X and Bi Y: S1P1 receptor inhibits kidney epithelial mesenchymal transition triggered by ischemia/reperfusion injury via the PI3K/Akt pathway. Acta Biochim Biophys Sin (Shanghai). 50:651–657. 2018.PubMed/NCBI View Article : Google Scholar
27	Silva MR, Chiamolera MI, Kasamatsu TS, Cerutti JM and Maciel RM: Thyrotoxic hypokalemic periodic paralysis, an endocrine emergency: Clinical and genetic features in 25 patients. Arq Bras Endocrinol Metabol. 48:196–215. 2004.(In Portuguese). PubMed/NCBI View Article : Google Scholar
28	Garber M, Guttman M, Clamp M, Zody MC, Friedman N and Xie X: Identifying novel constrained elements by exploiting biased substitution patterns. Bioinformatics. 25:i54–i62. 2009.PubMed/NCBI View Article : Google Scholar
29	Moreno-Estrada A, Gignoux CR, Fernández-López JC, Zakharia F, Sikora M, Contreras AV, Acuña-Alonzo V, Sandoval K, Eng C, Romero-Hidalgo S, et al: Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science. 344:1280–1285. 2014.PubMed/NCBI View Article : Google Scholar