title: An association study of CASQ1 gene polymorphisms and heat stroke.
abstract: Although molecular mechanisms of heat stroke under physiological and pathological conditions have not yet been elucidated, a novel disease-associated gene encoding a calcium-binding protein, calsequestrin-1 (CASQ1), was suggested relevant based on results from a transgenic murine model. Here, we show the association between single nucleotide polymorphisms (SNPs) of CASQ1 and physiological parameters for heat stroke from a study involving 150 patients. Pooled DNA from heat stroke patients were subjected to sequencing and 3 SNPs were identified. Genotypes were assigned for all patients according to g. 175A>G, one SNP which leads to a nonsynonymous substitution (N59D) in the first exon of human CASQ1 gene. We analyzed the genotypic data with a linear model based on significance scores between SNP (175A>G) and heat stroke parameters. As a result, we found a significant association between SNP A175G and heat stroke (P<0.05). Further bioinformatics analysis of the 1-Mb flanking sequence revealed the presence of two genes that encode DDB1 and CUL4 associated factor 8 (DCAF8), and peroxisomal biogenesis factor 19 (PEX19), respectively, which might be functionally related to CASQ1. Our results showed that the blood calcium of patients with allele D increased significantly, compared to patients with allele N (P<0.05), which may result from the decreased calcium in muscle, suggesting that N59D in CASQ1 might account for the dysfunction of CASQ1 in calcium regulation during heat stroke.
authors.affiliation: Department of Radiology, Chinese PLA Medical School, Beijing 100853, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Health Medicine, Beijing Electric Power Hospital, Beijing 100073, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiology, Chinese PLA Medical School, Beijing 100853, China. Electronic address: cjr.malin@vip.163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002155:Calsequestrin; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D018883:Heat Stroke / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C503129:CASQ1 protein, human; D002135:Calcium-Binding Proteins; D002155:Calsequestrin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C087343:PEX19 protein, human; D002118:Calcium
keywords: CASQ1; Heat stroke; Single nucleotide polymorphism