Association Between LRP1B Gene Polymorphism And DEACMP Susceptibility In Northern Henan

BackgroundMost of the acute carbon monoxide poisoning(ACMP)patients recover without any sequelae after effective treatment,whereas 10% to 30% of ACMP patients manifested a variety of neuropsychiatric symptoms,such as acute dementia and Parkinson’s syndrome,which is referred to as delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).The disease is commonly seen in middle-aged to elderly people,without gender bias,is characteristic of serious sickness,slow recovery,multiple complications,as well as poor prognosis.And the lack of clear and effective prediction and treatment measures have placed a heavy burden on patients and their families.Up to date,numerous previous studies on epidemiology,disease development,clinical characteristics,changes in cerebrospinal fluid and peripheral blood biochemicals have suggested genetic susceptibility in DEACMP.In this study,based on genome-wide association study(GWAS)and small sample validation,four SNPs loci(rs10183908,rs10496896,rs1541976,rs352985)of low-density lipoprotein receptor-related protein 1B(LRP1B)gene were screened and to revalidated their associations.ObjectivesTo investigate the correlation between four SNPs loci of LRP1 B gene(rs10183908,rs10496896,rs1541976,rs352985)and DEACMP,and to explore the susceptible gene in DEACMP.Methods1.The clinical data and blood samples of ACMP and DEACMP patients were collected from the database established by DEACMP research group since 1974.1200 Chineses Han subjects in northern Henan Province were recruited according to the diagnostic criteria,inclusion criteria and exclusion criteria of ACMP and DEACMP,and the clinical data and blood samples were collected from November,2006 to April,2019.2.The subjects were divided into ACMP group(784 cases)and DEACMP group(416 cases).The influential factors such as gender,education background as well as age between two groups were screened out for fair comparison,without any other impact factors.According to their education level,all subjects were divided into stratification,namely,primary school,secondary school and above,and illiteracy.3.3ml peripheral blood were collected from all subjects into sample tubes with EDTA anticoagulant.Blood was collected from ACMP patients within 24 hours after resuscitation,and blood was collected from DEACMP patients at 6a.m.to 8a.m.on the following day of admission.All blood samples were stored at-80℃.4.Based on our previous GWAS research results,four DEACMP-related SNPs loci of LRP1 B gene(rs10183908,rs10496896,rs1541976,rs352985)were selected as detection loci.The genetic association between LRP1 B gene polymorphism and DEACMP was verified with Mass ARRAY Time-of-Flight Mass Spectrometry(Sequenom Co.)5.The chi-square test of goodness of fit was used to test the genotypic distribution of Hardy-Weinderg equilibrium law;binary logistic regression was used to test the correlation between different groups.The statistics analysis was conducted with SPSS 22.0 statistical software,P< 0.05 was considered statistically significant.Results1.For rs10183908,the allele association analysis showed that allele frequency distribution of rs10183908 in DEACMP group and ACMP group were not significantly different(P>0.05).The results of correlation analysis of rs10183908 genotype and incidence of DEACMP under four genetic modes(codominant,dominant,recessive and hyperdominant)were as follows: under codominant model,AA vs AG P=0.638,OR=0.939(0.724,1.219),AA vs GG P=0.928,OR=0.984(0.690,1.403);under dominant genetic model,P=0.685,OR=0.951(0.744,1.214);under hyperdominant genetic model,P=0.636,OR=0.944(0.743,1.199);under recessive inheritance model,P=0.916,OR=1.018(0.735,1.410).There were no significant differences among four models.2.For rs10496896,the allele association analysis showed that allele frequency distribution of rs10496896 in DEACMP group and ACMP group were not significantly different(P>0.05).The results of correlation analysis of rs10496896 genotype and the incidence of DEACMP under four genetic modes(codominant,dominant,recessive and hyperdominant)were as follows: under codominant model,CC vs CT P=0.795,OR=0.966(0.744,1.254),CC vs TT P=0.930,OR=0.984(0.691,1.402);under dominant genetic model,P=0.812,OR=0.971(0.760,1.239);under hyperdominant genetic model,P=0.806,OR=0.971(0.764,1.233);under recessive inheritance model,P=0.987,OR=1.003(0.724,1.388).Significant differences were not noticed among four models.3.For rs1541976,the allele association analysis showed that allele frequency distribution of rs1541976 in DEACMP group and ACMP group were not significantly different(P>0.05).The results of correlation analysis of rs1541976 genotype and the incidence of DEACMP under four genetic modes(codominant,dominant,recessive and hyperdominant)were as follows: under codominant model,CC vs AC P=0.827,OR=0.971(0.748,1.261),CC vs AA P=0.750,OR=1.060(0.741,1.514);under dominant genetic model,P=0.954,OR=0.993(0.776,1.269);under hyperdominant genetic model,P=0.705,OR=0.955(0.752,1.213);under recessive inheritance model,P=0.657,OR=1.077(0.777,1.493).There were not any significant differences among four models.4.For rs352985,the allele association analysis showed that allele frequency distribution of rs352985 in DEACMP group and ACMP group were not significantly different(P>0.05).The results of correlation analysis between rs352985 genotype and the incidence of DEACMP under four genetic modes(codominant,dominant,recessive and hyperdominant)were as follows: under codominant model,AA vs AG P=0.796,OR=0.966(0.744,1.255);under dominant genetic model,P=0.333,OR=1.126(0.885,1.433);under hyperdominant genetic model,P=0.141,OR=0.835(0.657,1.062);there were not any significant differences;under codominant model,AA vs GG P=0.004,OR=1.644(1.173,2.306);under recessive inheritance model,P=0.001,OR=1.673(1.225,2.284),and significant differences were noticed(P<0.05).Conclusions1.LRP1 B gene rs352985/G is associated with the risk of DEACMP in autosomal under codominant and recessive inheritance model.2.Three SNPs loci of LRP1 B gene(rs10183908,rs10496896 and rs1541976)are not associated with the pathogenesis of DEACMP under four genetic modes.