The Association Study Of LRCH1 Gene Polymorphisms With Delayed Encephalopathy After Acute Carbon Monoxide Poisoning

BackgroundDelayed encephalopathy after acute carbon monoxide poisoning(DEACMP),also known as carbon monoxide poisoning psychosis,indicates that the patients recover after acute carbon monoxide poisoning,but demonstrate a series of neuropsychiatric symptoms,such as acute dementia,after recovery period of 2-60 days(normal or roughly normal false).DEACMP is one of serious organic psychosis,accounts for 10% ~ 30% of ACMP,affects the quality seriously on patients and their families due to slow recovery,multiple complications and poor prognosis,as well as the lack of clear and effective measures for prediction and treatment.Previous studies on cerebrospinal fluid and peripheral blood biochemicals in patients with DEACMP revealed the genetic predisposition.Based on our previous completed genome-wide association analysis of DEACMP-related single nucleotide polymorphism loci,we explored the possible relevance of SNP loci to the pathogenesis of DEACMP,in order to provide new ideas and molecular targets for prevention,diagnosis and treatment of DEACMP.ObjectivesBy means of searching the association of single nucleotide polymorphisms(rs1539177,rs17068697,rs9534475 and rs2236592)of Leucine-rich repeat and calponin homology domain-containing protein 1(LRCH1)with delayed encephalopathy after acute carbon monoxide poisoning,aims to discover the genetic susceptibility genes in the pathogenesis of DEACMP.Methods1.The blood samples were collected in fasting DEACMP patients at 6-8AM into EDTA tubes with anticoagulant in the following day after admission;the blood samples were collected in fasting ACMP patients within 24 h after full recovery from unconsciousness.3ml of venous blood in each patient was collected and refrigerated at-70?.2.We need to extract and identificate DNA of samples.3.The Sequenom MassArray SNP technique was used to verify LRCH1 gene polymorphism and DEACMP genetic susceptibility.Results1.For rs1539177: there were no significant differences in allele frequency distribution(Pobs =0.050346)between two groups.Under different genetic models(codominance inheritance,dominant inheritance,recessive inheritance),the association analysis results were Pobs=0.043729,OR=1.279(1.007-1.624)in codominance genetic mode,Pobs=0.018579,OR=1.511(1.070-2.133)in dominant genetic model,and Pobs=0.50527,OR=1.165(0.743-1.828)in recessive genetic model.2.For rs17068697: there were no significant differences in allele frequency distribution(Pobs =0.056602)between two groups.Under different genetic models(codominance inheritance,dominant inheritance,recessive inheritance),the association analysis results were Pobs =0.043125,OR=1.285(1.008-1.638)in codominance genetic model,Pobs=0.009228,OR=1.770(1.147-2.729)in dominant genetic model and Pobs=0.466963,OR=1.146(0.794-1.653)in recessive genetic model.3.For rs9534475: there were significant differences in allele frequency distribution(Pobs =0.038445,OR=1.273(1.013-1.601))between two groups.Under different genetic models(codominance inheritance,dominant inheritance,recessive inheritance),the association analysis results were Pobs =0.035878,OR=1.285(1.017-1.623)in codominance genetic model,Pobs =0.005935,OR=1.617(1.147-2.280)in dominant genetic model and Pobs=0.742672,OR=1.077(0.693-1.674)in recessive genetic model.4.For rs2236592: there were no significant differences in allele frequency distribution(Pobs=0.080373)between two groups.Under different genetic models(codominance inheritance,dominant inheritance,recessive inheritance),the association analysis results were Pobs =0.064827,OR=1.254(0.986-1.597)in codominance genetic model,Pobs=0.015784,OR=1.616(1.092-2.390)in dominant genetic model and Pobs=0.61508,OR=1.105(0.748-1.634)in recessive genetic model.Conclusions1.Based on autosomal codominance inheritance pattern and dominant genetic pattern,LRCH1 rs1539177,LRCH1 rs17068697,LRCH1 rs9534475 polymorphism was associated with DEACMP.2.Based on autosomal dominant inheritance pattern,LRCH1 rs2236592 polymorphism was associated with DEACMP.3.The A allele could lead to higher DEACMP risk.4.LRCH1 SNP may be the molecular genetic basis of DEACMP.