A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis

Jongjaroenprasert, Wallaya; Phusantisampan, Theerawut; Mahasirimongkol, Surakameth; Mushiroda, Taisei; Hirankarn, Nattiya; Snabboon, Thiti; Chanprasertyotin, Suwannee; Tantiwong, Puntip; Soonthornpun, Supamai; Rattanapichart, Paninee; Mamanasiri, Sunee; Himathongkam, Thep; Ongphiphadhanakul, Boonsong; Takahashi, Atsushi; Kamatani, Naoyuki; Kubo, Michiaki; Nakamura, Yusuke

doi:10.1038/jhg.2012.20

Cited by 30 publications

(21 citation statements)

References 22 publications

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“…The study population were compiled from previously published genome-wide association studies (GWAS) in Thai individuals [15], [16], [17], [18], [19], which were generated under collaborations between the Ministry of Public Health, Thailand, Thailand Center of Excellence for Life Sciences (TCELS), and the RIKEN Center for Genomic Medicine (CGM), Japan (Table 1), and CNV data of 11 different ethnic groups publicly available through the HapMap3 project (Table S1 in File S1) [14]. This study was approved by a Committee on Human Rights Related to Research Involving Human Subjects, Faculty of Medicine Ramathibodi Hospital, Mahidol University.…”

Section: Methodsmentioning

confidence: 99%

Copy Number Variation in Thai Population

et al. 2014

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Copy number variation (CNV) is a major genetic polymorphism contributing to genetic diversity and human evolution. Clinical application of CNVs for diagnostic purposes largely depends on sufficient population CNV data for accurate interpretation. CNVs from general population in currently available databases help classify CNVs of uncertain clinical significance, and benign CNVs. Earlier studies of CNV distribution in several populations worldwide showed that a significant fraction of CNVs are population specific. In this study, we characterized and analyzed CNVs in 3,017 unrelated Thai individuals genotyped with the Illumina Human610, Illumina HumanOmniexpress, or Illumina HapMap550v3 platform. We employed hidden Markov model and circular binary segmentation methods to identify CNVs, extracted 23,458 CNVs consistently identified by both algorithms, and cataloged these high confident CNVs into our publicly available Thai CNV database. Analysis of CNVs in the Thai population identified a median of eight autosomal CNVs per individual. Most CNVs (96.73%) did not overlap with any known chromosomal imbalance syndromes documented in the DECIPHER database. When compared with CNVs in the 11 HapMap3 populations, CNVs found in the Thai population shared several characteristics with CNVs characterized in HapMap3. Common CNVs in Thais had similar frequencies to those in the HapMap3 populations, and all high frequency CNVs (>20%) found in Thai individuals could also be identified in HapMap3. The majorities of CNVs discovered in the Thai population, however, were of low frequency, or uniquely identified in Thais. When performing hierarchical clustering using CNV frequencies, the CNV data were clustered into Africans, Europeans, and Asians, in line with the clustering performed with single nucleotide polymorphism (SNP) data. As CNV data are specific to origin of population, our population-specific reference database will serve as a valuable addition to the existing resources for the investigation of clinical significance of CNVs in Thais and related ethnicities.

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Section: Methodsmentioning

confidence: 99%

Copy Number Variation in Thai Population

et al. 2014

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“…11 They do not have a known calcium or sodium channelopathy, but there is genetic data to implicate potassium channel mutations. 24 In addition, patients without channelopathies can develop a subacute proximal myopathy in the setting of severe hypokalemia (serum K <2.5 mEq/L). 25,26 Hyperkalemic periodic paralysis Hyperkalemic PP is an autosomal dominant SCN4A channelopathy that is allelic to PC and typically begins in the first decade.…”

Section: Hypokalemic Periodic Paralysismentioning

confidence: 99%

Electrodiagnosis of Myotonic Disorders

Hehir

Logigian

2013

Physical Medicine and Rehabilitation Clinics of North America

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“…During the genotyping and matching of our cohort of TPP and controls (TWP) for ABCC8 variant, two Asian GWAS studies were published, indicating that a new TPP locus (17q24.3) has emerged (Cheung et al 2012, Jongjaroenprasert et al 2012. None of the genes related to insulin response is found within this locus, indicating that ABCC8 hyperinsulinaemia genetic predisposition is either an additional phenotype-modulating trait or an ethnic-dependent linked genetic association.…”

Section: Discussionmentioning

confidence: 99%

The insulin-sensitivity sulphonylurea receptor variant is associated with thyrotoxic paralysis

Rolim¹,

Lindsey²,

Kunii³

et al. 2014

Journal of Molecular Endocrinology

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Thyrotoxicosis is the most common cause of the acquired flaccid muscle paralysis in adults called thyrotoxic periodic paralysis (TPP) and is characterised by transient hypokalaemia and hypophosphataemia under high thyroid hormone levels that is frequently precipitated by carbohydrate load. The sulphonylurea receptor 1 (SUR1 (ABCC8)) is an essential regulatory subunit of the b-cell ATP-sensitive K C channel that controls insulin secretion after feeding. Additionally, the SUR1 Ala1369Ser variant appears to be associated with insulin sensitivity. We examined the ABCC8 gene at the single nucleotide level using PCR-restriction fragment length polymorphism (RFLP) analysis to determine its allelic variant frequency and calculated the frequency of the Ala1369Ser C-allele variant in a cohort of 36 Brazilian TPP patients in comparison with 32 controls presenting with thyrotoxicosis without paralysis (TWP). We verified that the frequency of the alanine 1369 C-allele was significantly higher in TPP patients than in TWP patients (61.1 vs 34.4%, odds ratio (OR)Z3.42, PZ0.039) and was significantly more common than the minor allele frequency observed in the general population from the 1000 Genomes database (61.1 vs 29.0%, ORZ4.87, P!0.005). Additionally, the C-allele frequency was similar between TWP patients and the general population (34.4 vs 29%, ORZ1.42, PZ0.325). We have demonstrated that SUR1 alanine 1369 variant is associated with allelic susceptibility to TPP. We suggest that the hyperinsulinaemia that is observed in TPP may be linked to the ATP-sensitive K C /SUR1 alanine variant and, therefore, contribute to the major feedforward precipitating factors in the pathophysiology of TPP.

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A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis

Cited by 30 publications

References 22 publications

Copy Number Variation in Thai Population

Copy Number Variation in Thai Population

Electrodiagnosis of Myotonic Disorders

The insulin-sensitivity sulphonylurea receptor variant is associated with thyrotoxic paralysis

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