| BackgroundThe severest complication of the survivors after acute carbon monoxide poisoning(ACMP)is delayed encephalopathy after acute carbon monoxide poisoning(DEACMP)which is a serious organic psychoses.Among all with ACMP patients,the incidence of DEACMP ranges from 10% to 30%.Those patients are usually in serious condition,with more complications,slow recovery and poor prognosis.The domestic and foreign studies of epidemiology,clinical characteristics,law of disease development,neuroimage and biochemical level of blood and cerebrospinal fluid in patients with DEACMP have revealed the underlying genetic susceptibility.Based on previously screened DEACMP-related single nucleotide polymorphisms(SNPs)loci from our group,as well as the pathological characteristics of DEACMP,we explore the possible correlation of SNP loci in myelin basic protein(MBP)gene to the pathogenesis of DEACMP,with goal of providing new insight for prediction,prevention and diagnosis of DEACMP.ObjectivesTo evaluate the association of MBP gene's SNPs(rs470555,rs470724,rs4890785,rs595997,rs76452994,and rs921336)with DEACMP.Our objective was to explore DEACMP associated genetic susceptibility genes.Methods1.The study cases were recruited from the Han population in Northern Henan Province from November 2006 to April 2019.All enrolled subjects meet the Diagnostic Criteria of Occupational Acute Carbon Monoxide Poisoning(GBZ23-2002).All DEACMP patients meet DEACMP diagnose criteria based on Zhao,Xiangzhi etc's diagnose and 8th Edition of " Internal Medicine".There are 416 cases in DEACMP group,and 785 cases in ACMP group.Specifically,for rs470555 loci study,there are 780 cases of ACMP(female 365 cases,male 415 cases)and 415 cases of DEACMP(female 172 cases,male 243 cases).For rs470724 loci study,there are 779 cases of ACMP(female 367 cases,male 412 cases)and 416 cases of DEACMP(female 172 cases,male 244 cases).For rs4890785 Loci study,there are 784 cases of ACMP(female 369 cases,male 415 cases)and 415 cases of DEACMP(female 172 cases,male 243 cases).For rs595997 loci study,there are 781 cases of ACMP(female 368 cases,male 413 cases)and 414 cases of DEACMP(female 172 cases,male 242 cases).For rs76452994 Loci study,there are 783 ACMP cases(female 368 cases,male 415 cases)and 415 DEACMP cases(female 172 cases,male 243 cases).For rs921336 Loci study,there are 784 ACMP cases(female 369 cases,male 415 cases)and 415 DEACMP cases(male 243 cases,female 172 cases).All enrolled subjects were aged 40 or over.2.The 3ml blood specimens of all subjects are obtained from peripheral vein,collected in EDTA anticoagulant tube,and stored in-80? refrigerator.In ACMP cases,the blood specimens were collected within 24 hours after fully conscious achieved by successful resuscitation.In DEACMP cases,blood specimens were collected from 6 to 8AM on the second day of hospitalization.DNA extraction in all blood specimens was performed by using DNA extraction kit(spin column type)from TIANGEN company.3.Based on previous study on genome-wide association study(GWAS)from our group,and research on relevant literature,we screened out six SNPs loci on DEACMP related MBP gene as testing targets(rs470555,rs470724,rs4890785,rs595997,rs76452994,and rs921336).The MBP gene polymorphism and DEACMP genetic susceptibility were detected by using ionization time of flight mass spectrometry technique provided by Sequenom company MassArray technique.4.The distribution of genotypes in conformty with Hardy-Weinderg Law was analyzed by Goodness-of-Fit Chi-Square test;association analysis between groups was analyzed by Binary logistic regression test.All data were analyzed using SPSS 19.0 statistic.Statistically significant difference is defined by P<0.05.Results1.For rs470755 loci in MBP gene: under the model of codominant inheritance,dominant inheritance,overdominant inheritance and recessive inheritance,the results of correlation analysis on rs470755 genotype and DEACMP are listed as following: in codominant genetic model [AA vs AT P=0.915,OR=0.986(0.761,1.277),AA vs TT P =0.796,OR=1.049(0.731,1.504)],in dominant genetic model [P = 0.992,OR=1.001(0.786,1.276)],in overdominant genetic model [P = 0.826,OR=0.974(0.766,1.237)] and in recessive genetic model [P = 0.747,OR=1.056(0.756,1.476)].All differences are not statistically significant.The rs470555 allele frequency and genotype distributions in both DEACMP group and ACMP group are not statistically significant(P>0.05).2.For rs470724 in MBP gene: under the model of codominant inheritance,dominant inheritance,overdominant inheritance and recessive inheritance,the results of correlation analysis on rs470724 genotype and DEACMP are listed as following: in codominant genetic model [CC vs CT P=0.713,OR=0.953(0.737,1.232),CC vs TT P=0.674,OR=1.084(0.748,1.566)],in dominant genetic model [P=0.883,OR=0.982(0.772,1.249)],in overdominant genetic model [P = 0.582,OR=0.935(0.735,1.188)] and in recessive genetic model [P =0.556,OR=1.109(0.785,1.568)].All differences are not statistically significant.The rs470724 allele frequency and genotype distributions in both DEACMP group and ACMP group are not statistically significant(P>0.05).3.For rs4890785 in MBP gene: under the model of codominant inheritance,dominant inheritance,overdominant inheritance and recessive inheritance,the results of correlation analysis on rs4890785 genotype and DEACMP are listed as following: in codominant genetic model[CC vs CT = 0.851,OR=1.024(0.797,1.316),CC vs TT P=0.166,OR=1.488(0.846,2.619)],in dominant genetic model[P = 0.594,OR=1.068(0.839,1.359)],in overdominant genetic model[P = 0.582,OR=0.935(0.735,1.188)]and in recessive genetic model [P =0.169,OR=1.475(0.845,2.573)].All differences are not statistically significant.The rs4890785 allele frequency and genotype distributions in both DEACMP group and ACMP group are not statistically significant(P>0.05).4.For rs595997 in MBP gene: under the model of codominant inheritance,dominant inheritance,overdominant inheritance and recessive inheritance,the results of correlation analysis on rs595997 genotype and DEACMP are listed as following: in codominant genetic model[AA vs AG P= 0.112,OR=1.259(0.947,1.673),AA vs GG P =0.531,OR=1.116(0.793,1.570)],in dominant genetic model[P=0.159,OR=1.213(0.927,1.587)],in overdominant genetic model[P = 0.136,OR=1.199(0.944,1.522)]and in recessive genetic model [P=0.788,OR=0.961(0.722,1.281)].All differences are not statistically significant.The rs595997 allele frequency and genotype distributions in both DEACMP group and ACMP group are not statistically significant(P>0.05).5.For rs76452994 in MBP gene: under the model of codominant inheritance,dominant inheritance,overdominant inheritance and recessive inheritance,the results of correlation analysis on rs76452994 genotype and DEACMP are listed as following: in codominant genetic model[CC vs CG P = 0.001,OR=1.587(1.198,2.102)],in dominant genetic model [P= 0.001,OR=1.564,(1.193,2.051)],and in overdominant genetic model[P = 0.001,OR=1.572(1.188,2.079)],significant differences are noticed;in codominant genetic model [CC vs GG P=0.429,OR=1.363(0.630,2.947)] and in recessive genetic model[P = 0.608,OR=1.222(0.567,2.634)],there are not significant differences.The rs79452994 genotype and allele frequency distributions in both DEACMP group and ACMP group are not statistically significant(P>0.05).According to gender,in both DEACMP group and ACMP group,there are not statistically significant in the genotype distribution and allele frequency of rs76452994 in the male group(P>0.05),but there are statistically significant in the female group(P<0.05).6.For rs921336 in MBP gene: under the model of codominant inheritance,dominant inheritance,overdominant inheritance and recessive inheritance,the results of correlation analysis on rs921336 genotype and DEACMP are listed as following: in codominant genetic model[GG vs GT P=0.018,OR=1.355(1.053,1.744)],in dominant genetic model[P=0.012,OR=1.362(1.071,1.733)],and in overdominant genetic model[P=0.048,OR=1.273(1.002,1.617)],significant differences are noticed;in codominant genetic model [GG vs TT P=0.111,OR=1.394(0.925,2.101)] and in recessive genetic model [P = 0.608,OR=1.222(0.567,2.634)],there are not significant differences.The rs921336 genotype and allele frequency distributions in both DEACMP group and ACMP group are not statistically significant(P>0.05).According to gender,in both DEACMP group and ACMP group,there are statistically significant in the genotype distribution and allele frequency of rs921336 in both the male group and the female group(P<0.05).Conclusions1.Under the model of codominant,dominant and overdominant inheritance,the MBP gene rs921336/T polymorphism was associated with DEACMP risk.2.Under the model of codominant,dominant,and overdominant inheritance,the MBP gene rs76452994/G polymorphism was associated with the female DEACMP risk.3.Under all genetic models,the four SNPs loci of the MBP gene,rs470555,rs470724,rs4890785 and rs595997,were not associated with DEACMP. |
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