Association Of The Nrf2 Gene Nucleotide Polymorphism With Oxidative Stress And AMS

Objects:1. To observe the relationship between oxidative stress reaction and acute mountain sickness(AMS) as well as the severity after acute plateau exposure;2. To discuss the correlation between Nrf2 gene single nucleotide polymorphisms( SNPs) and AMS, aiming at providing scientific evidences for the pathogenetic mechanism and genetic screening in AMS.Methods:1. The relationship between oxidative stress and AMSFollowing with the inclusion and exclusion criteria, 134 volunteers were included. Using the method of nested case- control study, firstly, we collected demographic information in the plain area, secondly, the Lake Louise scoring and blood samples were gathered after reached the plateau, finally we tested the concentration of SOD and MDA in plasma and organized the collection information to analysis the relationship between SOD, MDA and onset of AMS as well as the severity.2. The relationship between Nrf2 gene SNPs and AMSFollowing with the inclusion and exclusion criteria, 603 volunteers were included. Similarly, we collected demographic information and blood samples in the plain area, gathered the Lake Louise scoring and physiological parameter such as blood pressure, heart rate and so on after reached the plateau, finally we detected the genotyping and organized the collection information to analysis the relationship between SNPs in Nrf2 gene and onset of AMS as well as the severity.Result:1. The concentrations of SOD in plasma was significantly lower in AMS group(1.31±0.82 ug/ml vs 1.71±0.88 ug/ml,P=0.016); and the concentrations of MDA was much higher than control group(6.90±2.31 ng/ml vs 5.83±2.71 ng/ml,P=0.025); but there were no significant differences for further subgroup analysis among mild-AMS, severe-AMS and control groups(Pcorrection>0.017).2. There were statistically significant differences in heart rate and SaO2: comparing with control group, AMS group had higher heart rate(P =0.01) and lower SaO2(P <0.01);3. The rate of successful detection were larger than 96% of rs10497511、rs1962142、rs2364722 and rs6721961 in Nrf2 gene, which was respectively detected the C/T, T/C, G /A and T/G genotype, and each genotype was in accordance with the Hardy-Weinberg equilibrium in the total population, the case group and control group(P>0.05); the C allele of rs1962142 in case group was significantly higher than the control and the difference was statistically significant(P=0.0032); the distribution of C/C genotype was higher than C/T and T/T genotype, and there was a statistical significance between C/C genotype and C/T genotype(Pcorrection =0.01<0.017); subgroup analysis showed a statistically significant difference of C allele between mild-AMS and control group(Pcorrection =0.009<0.017); after application of unconditioned Logistic regression to calibrate demographic information and physiological parameters, dominant model suggested that C/C genotype and(C/T + T/T) genotypes had a significant difference in case and control group(OR=1.67,95%CI 1.18-2.33, Pcorrection =0.0036<0.0071);but there were no statistical differences showed in allele frequency, genotype and genotype models in rs10497511、rs2364722 and rs6721961(P>0.05);three haplotypes were built by rs10497511、rs2364722 and rs6721961 included in TGG, CAT and TAG, however, no statistically differences were showed in case and control group(P>0.05).Conclusions:1. There was a correlation between plasma concentration of SOD and MDA and AMS: people with AMS had lower SOD concentration and higher MDA concentration in plasma than those without AMS;2. The crowd with AMS had higher heart rate and lower SaO2;3. Nrf2 gene mutation of C allele in rs1962142 locus related to AMS, which might be an independent risk factor for AMS and the one who carried in C/C genotype was more susceptible to AMS than the C/T genotype people.