| BackgroundKnown as the secondary disease of acute carbon monoxide poisoning (ACMP), the pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is still poorly understood. And it featured damaged central nervous system, demonstrating cognitive disorder, Parkinson syndrome. According to researches conducted both at home and abroad on DEACMP cerebrospinal fluid and blood biochemicals as well as our previous DEACMP genome-wide SNPs genotyping chip screening results, the DEACMP was possibly related to genetic variation. The investigation of DEACMP gene susceptibility in this thesis will be helpful to improve its pathogenesis, so as to provide genetic basis for the development of drugs and the introduction of new treatment methods.ObjectivesTo investigate the association of low-density lipoprotein receptor-related protein1B (LRP1B) gene polymorphisms (rs10183908, rs1541976) with delayed encephalopathy after acute carbon monoxide poisoning, and to explore the influences of DEACMP gene susceptibility and environmental factors.Methods1. For rs1541976study,231patients from Han population (138male,93female) in Northern Henan Province were eligible once they met the criteria on DEACMP in book of "Internal Medicine, sixth Edition" and Zhao Xiangzhi’s;267patients from Han population (117male,150female) at the same areas were selected as ACMP group; for rs10183908study,231patients from Han population (136male,95female) in Northern Henan Province were recruited,264patients from Han population (116male,148female) at the same areas were selected as ACMP group; both ACMP patients met the requirements of "national occupational standards for acute carbon monoxide poisoning GB8781-88". The patients in two groups were over40years of age.2.3ml cubital vein blood was collected in EDTA anticlotting tubes from fasting subjects. The blood samples were collected in DEACMP patients at6AM to8AM, and1d after ACMP patients were fully conscious. Then the samples were stored at-70℃. The DNA in all samples were extracted with DNA extration kit from TIANGEN corporation.3. The rs1541976and rs10183908which were related to nerve function were determined by Polymerase chain reaction-restriction fragment polymorphism(PCR-RELP) and genom sequencing (ABI3730DNA Sequences, GENEW1Z, Inc), respectively.4. The statistic analysis were carried out using SPSS16.0for windows, including the goodness-of-fit chi-square test, analysis of genotype distribution in accordance with Hardy-Weinderg equilibrium, and X2test for correlation analysis.Results1. For rs1541976in LRP1B gene:the genotype distributions in both DEACMP group and ACMP group were significantly different (P=0.000). so was the allele frequency distribution of A and C(P=0.007). After stratification by gender, the general genotype distribution in females in both groups was not significantly different (P=0.134). either was allele frequency distribution (P=0.271); the general genotype distribution in males in both groups was significantly different (P=0.003), so was allele frequency distribution (P=0.025). The genotype distribution in both male and females in ACMP group was not significantly different (P=0.724), either was allele frequency distribution (P＝O.686):The genotype distribution in both male and females in DEACMP group was significantly different (P=0.044), in contrast to non-statistically different allele frequency distribution (P=0.841).2. For rs10183908in LRP1B gene:the genotype distributions in both DEACMP group and ACMP group were not significantly different (P＝0.438), either was the allele frequency distribution(P=0.294). After stratification by gender, the general genotype distribution in females in both groups was not significantly different (P=0.301), either was allele frequency distribution (P=0.128); the general genotype distribution in males in both groups was not significantly different (P=0.776), either was allele frequency distribution (P=0.661). The genotype distribution in both male and females in ACMP group was not significantly different (P=0.107), whereas the allele frequency distribution was not significantly different (P=0.043); The genotype distribution in both male and females in DEACMP group was not significantly different (P=0.552), either was allele frequency distribution (P=0.305).Conclusion1. The LRP1B polymorphism was associated with DEACMP, suggesting the LRP1B rs1541976polymorphism may be the basis of molecular genetics of DEACMP.2. In the LRP1B rs1541976gene, the male ACMP patients might have increased risk of DEACMP, and A/C genetype also could lead to higher DEACMP risk, especially the male ACMP patients with C allele. It suggested that LRP1B gene polymorphism might be gender-subject molecular genetic susceptibility.3. The association of LRP1B rs10183908polymorphism with DEACMP has not yet been found, the thought of LRP1B rs10183908to be DEACMP susceptibility gene was not supported. |
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