LRCH1 polymorphisms linked to delayed encephalopathy after acute carbon monoxide poisoning identified by GWAS analysis followed by Sequenom MassARRAY® validation

Gu, Jingjing; Zeng, Jiao; Wang, Xi; Gu, Xuefan; Zhang, Xiaoli; Ping, Zhang; Zhang, Fan; Han, Yusheng; Han, Yazhou; Zhang, Hongxing; Li, Wenqiang; Gu, Renjun

doi:10.1186/s12881-019-0931-7

“…The study confirmed that two SNPs (rs11845632, rs2196447) in axon protein 3 gene (NRXN3) correlated with DEACMP [ 18 ] and that there was a correlation between rs1784594 in the Parkin gene and DEACMP. We also found that allele A of rs1784594 may increase the risk of DEACMP in female ACMP patients [ 25 ], that LRP1B gene rs1541976 polymorphism is a potential susceptible factor of DEACMP [ 26 ], and that LRCH1 (rs1539177, rs17068697, rs9534475, and rs2236592) is associated with DEACMP [ 27 ]. These results suggest that some ACMP patients are specifically sensitive to acute carbon monoxide poisoning due to polygenic defects, which leads to the initiation of a central nervous system's autoimmune response that attacks the corresponding target cells, leading to the relevant clinical changes.…”

Section: Discussionmentioning

confidence: 99%

Association between Neuron-Specific Enolase Gene Polymorphism and Delayed Encephalopathy after Acute Carbon Monoxide Poisoning

Xu

¹

,

Liu

²

,

Zhao

³

et al. 2020

Behavioural Neurology

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Objective. The aim of this study is to explore the relationship between neuron-specific enolase (NSE) gene polymorphism and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) and provide a theoretical basis for DEACMP pathogenesis, diagnosis, and prognosis. Methods. To investigate this relationship, we screened 6 NSE single nucleotide polymorphisms (SNPs), based on the results of the previous genome-wide association studies (GWAS). A total of 1,201 patients, including 416 in the DEACMP group and 785 in the acute carbon monoxide poisoning (ACMP) group, were detected by the Sequenom MassARRAY® method. The genotype frequencies and alleles of the 6 NSE SNPs (rs2071074, rs2071417, rs2071419, rs11064464, rs11064465, and rs3213434) were compared using different genetic models. Results. In the SNPs rs2071419 and rs3213434, we found that the genotypes and allele frequencies in the two groups significantly correlated with the grouping of patients ( χ 2 = 6.596 , p = 0.037 ; χ 2 = 8.769 , p = 0.012 ). The haplotypes GGTTTC and CCTTTC of ACMP and DEACMP were different ( χ 2 = 6.563 , p = 0.010 ; χ 2 = 4.151 , p = 0.042 ). We also observed that rs2071419 and rs3213434 significantly correlated with DEACMP-increased risk in the dominant, codominant, and overdominant genetic models. In addition, we speculated that the C allele of the rs2071419 polymorphism and the T allele of the rs3213434 polymorphism in NSE may increase the DEACMP risk ( p = 0.011 , p = 0.006 ). Conclusions. The results show that rs2071419 and rs3213434 are susceptible sites of DEACMP. The NSE C allele of rs2071419 and T allele of rs3213434 and the haplotypes GGTTTC and CCTTTC may be risk factors for DEACMP.

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“…The score is proportional to cognitive function. Illiteracy <16, secondary school or above <24, primary school <20 points with cognitive impairment [5][6][7] .…”

Section: Score Standardmentioning

confidence: 99%

Effects of Early Ulinastatin Injection Combined With Hyperbaric Oxygen on Myocardial Enzymes and Cognitive Function in Patients with Acute Moderate and Severe Carbon Monoxide Poisoning

Wang¹,

Xiong²,

Zhao³

2021

ijps

0

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Wang et al.: Combined Effect of Ulinastatin Injection and Hyperbaric Oxygen in Carbon Monoxide Poisoning PatientsTo observe the effect of early ulinastatin injection combined with hyperbaric oxygen on myocardial enzyme and cognitive function in patients with acute moderate and severe carbon monoxide poisoning. From May 2017~December 2020, 104 patients with acute carbon monoxide poisoning coma were divided into groups according to their treatment plan, 52 cases in the control group were treated with hyperbaric oxygen. Ulastatin group 52 cases were treated with early ulastatin injection combined with hyperbaric oxygen. The curative effect and incidence of delayed encephalopathy were counted, the average recovery time of the two groups was recorded, the changes of Hasegawa dementia scale score and Mini mental state examination score were compared between the two groups and the differences of blood gas index, myocardial enzyme index, and oxidative stress index and blood viscosity were detected. Ulinastatin group had higher efficacy than the control group (p<0.05). The blood oxygen partial pressure and superoxide dismutase increased in ulinastatin group and control group. The blood carbon dioxide partial pressure, creatine kinase, creatine kinase isoenzyme, aspartate aminotransferase, lactate dehydrogenase and malondialdehyde, catalase, lipid peroxide decreased. The oxygen partial pressure, superoxide dismutase of ulinastatin group after treatment was higher than that of control group, carbon dioxide partial pressure, myocardial enzyme index and malondialdehyde, catalase, lipid peroxide were lower than those of control group (p<0.05).The whole blood (high and low cut) viscosity and plasma viscosity of ulinastatin group and control group decreased, the Hasegawa dementia scale score and Mini mental state examination score increased and the blood viscosity of ulinastatin group was lower than that of control group after treatment and the Hasegawa dementia scale score and Mini mental state examination score were higher than that of control group (p<0.05).Average recovery time of ulinastatin group was shorter than that of control group and the incidence of delayed encephalopathy was lower than that of control group (p<0.05). Early ulinastatin injection combined with hyperbaric oxygen in the treatment of acute carbon monoxide poisoning coma can reduce oxidative stress injury, reduce myocardial enzyme expression and blood viscosity, improve blood gas index, promote patients to wake up and reduce the occurrence of delayed encephalopathy. It is worthy of clinical recommendation.

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“…SNPs in LRCH1 have been associated with a higher risk to develop osteoarthritis, although not all studies could confirm these findings (Spector et al, 2006;Snelling et al, 2007;Jiang et al, 2008;Panoutsopoulou et al, 2017). SNPs in LRCH1 are also allocated to an increased risk of delayed encephalopathy after acute carbon monoxide poisoning (Gu et al, 2019). Pigs with SNPs in LRCH3 are more susceptible to infections with Escherichia coli (E. coli) and cows with SNPs in LRCH3 have a higher susceptibility to Mycobacterium avium ssp.…”

Section: Genomic Analysesmentioning

confidence: 99%

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

Rivière

¹

,

Bader

²

,

Pogoda

³

et al. 2020

Front. Cell Dev. Biol.

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Actin-dependent leukocyte trafficking and activation are critical for immune surveillance under steady state conditions and during disease states. Proper immune surveillance is of utmost importance in mammalian homeostasis and it ensures the defense against pathogen intruders, but it also guarantees tissue integrity through the continuous removal of dying cells or the elimination of tumor cells. On the cellular level, these processes depend on the precise reorganization of the actin cytoskeleton orchestrating, e.g., cell polarization, migration, and vesicular dynamics in leukocytes. The fine-tuning of the actin cytoskeleton is achieved by a multiplicity of actin-binding proteins inducing, e.g., the organization of the actin cytoskeleton or linking the cytoskeleton to membranes and their receptors. More than a decade ago, the family of leucine-rich repeat (LRR) and calponin homology (CH) domain-containing (LRCH) proteins has been identified as cytoskeletal regulators. The LRR domains are important for protein-protein interactions and the CH domains mediate actin binding. LRR and CH domains are frequently found in many proteins, but strikingly the simultaneous expression of both domains in one protein only occurs in the LRCH protein family. To date, one LRCH protein has been described in drosophila and four LRCH proteins have been identified in the murine and the human system. The function of LRCH proteins is still under investigation. Recently, LRCH proteins have emerged as novel players in leukocyte function. In this review, we summarize our current understanding of LRCH proteins with a special emphasis on their function in leukocyte biology.

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LRCH1 polymorphisms linked to delayed encephalopathy after acute carbon monoxide poisoning identified by GWAS analysis followed by Sequenom MassARRAY® validation

Cited by 6 publications

References 17 publications

Association between Neuron-Specific Enolase Gene Polymorphism and Delayed Encephalopathy after Acute Carbon Monoxide Poisoning

Association between Neuron-Specific Enolase Gene Polymorphism and Delayed Encephalopathy after Acute Carbon Monoxide Poisoning

Effects of Early Ulinastatin Injection Combined With Hyperbaric Oxygen on Myocardial Enzymes and Cognitive Function in Patients with Acute Moderate and Severe Carbon Monoxide Poisoning

Structure and Emerging Functions of LRCH Proteins in Leukocyte Biology

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