| Objective With the development of world population aging,Alzheimer’s disease now has been reported to be the “third killer" after the cardiovascular and cerebrovascular diseases and tumors,which severely affect lives and health of the elderly people.Currently,there has about 50 million people that are suffering from this disease all over the world,and by 2050,the number of patients with AD will increase by three times.The Late-onset Alzheimer’s disease(LOAD)is the most common type of AD and the incidence of LOAD accounted for more than 90% of the total,which is caused by genetic mutations and environmental factors.The genetic factors have a significant impact on the incidence of LOAD.LOAD is a kind of polygenic inheritance disease,and its heredity is complex and heterogeneous.So far,the Apoe gene is considered as the only putative susceptibility gene that is associated with the risk of LOAD,which plays an important role in the development and progression of LOAD.Researches show that the inheritance of LOAD is very high and can reach to 58%-79%,however the Apoe ε4 allele proportion of LOAD patients is less than 50%.Thus,despite the vital importance of Apoeε4 in LOAD,it can not constitute a sufficient and necessary condition for LOAD.In view of this,it might tell us that the real decider of AD genetic susceptibility is still to be studied and there may be other candidate genes dominate the development of LOAD beyond Apoe.A recent meta-analysis finds that encoding NME/NM23 family member gene 8(NME8)(rs2718058)that located on chromosome 7 has a strong association with the risk of LOAD,but the study sample is restricted to Caucasian population.The human NME8 gene is located in the 7p14.1 region and NME8 gene polymorphism plays an important role in the nervous system,which is involved in the formation of cytoskeleton,axonal transport and antioxidant responses.Considering that the genetic heterogeneity,gene mutation as well as gene frequency in different races may be variable,the impact of genes on the risk of LOAD will be different either.So far,the association between NME8 gene polymorphism(rs2718058)and LOAD disease has not been confirmed in northern Chinese Han population.Therefore,the aim of this study is to clarify the association between NME8 gene polymorphism and the risk of LOAD in northern Han Chinese population.Methods In this study,a case-control study is conducted in 984 sporadic late-onset AD(LOAD)patients and 1354 healthy controls that are matched for sex and age in a large north Han Chinese individuals.One selected functional loci rs2718058,adjacent to geneNME8 on chromosome 7p14.1,is genotyped by the high-throughput SNPscan technology.On the other hand,the Apoe E gene is genotyped by polymerase chain reaction-ligase detection reaction(PCR-LDR)technique.Then we analyze the relation between rs2718058 locus and LOAD using the statistical method of chi square test and Logistic correlation regression analysis.The association of the genotype and allele frequencies between LOAD patients and healthy controls with the risk of LOAD is elucidated.In order to balance the influence of racial differences and sample size,we sort out the all the international published case-control studies about rs2718058 locus and conduct a meta-analysis(29060 of individuals are included in the study group and the control group are composed of 53653 individuals)to further explain the association between NME8 and the northern Han Chinese.The sample is consisted of Caucasian,Hispanic,in Southern Han Chinese population and northern Han Chinese.Result We study 2338 ethnic Northern Han Chinese subjects including a total of 984 subjects with probable LOAD and 1354 healthy control subjects.No statistically significant differences are observed for age(age at onset for LOAD and age at examination for controls)and gender(P>0.05)between LOAD case group and control group.The MMSE scores are significantly less in AD patients than in controls(P < 0.001).As expected,the Apoe ε4 allele frequency is also significantly different between AD patients and controls(P< 0.001,OR=2.422,95%CI=1.970~2.977).The genotype and allele distributions of rs2718058 in the cases and controls in the total sample and after stratification for Apoe ε4 allele are showed no statistical significance.Distributions of the rs2718058 genotypes in controls is in the Hardy-Weinberg equilibrium(P > 0.05)and that in case group is not in the Hardy-Weinberg equilibrium(P=0.02361).The frequency of the minor allele G is higher in LOAD compared to controls(22.9% versus 21.3%).Our study shows that there is no significant difference between LOAD patients and controls(OR = 1.072,95% CI = 0.932~1.234,P = 0.331).Similarly,the genotypes are not significantly different from LOAD patients and controls(P=0.181).What’s more,when these data are stratified by the Apoe ε4 status,there still has no evident differences in the genotypic or allelic distributions between AD cases and controls(Table 2).Furthermore,the results of the multivariate logistic regression with adjustment for age,gender,and the carriage of Apoe ε4 allele also fail to reveal any significant differences between LOAD and controls(Dominant: OR = 1.091,95% CI = 0.919~1.295,P = 0.319;Recessive: OR = 1.341,95% CI = 0.927~1.941,P = 0.119;and Additive: OR = 1.106,95%CI =0.961~1.273,P=0.160).To the contrary,a meta-analysis combined the results from Caucasian population,south Han Chinese population and North Han Chinese population together is conducted on the association of rs2718058 and LOAD in a sample of 82513 individuals,we found a close relation between 2718058 with LOAD risk(OR=1.08,95%CI=1.05~1.11)(Figure1)without evident analysis heterogeneity(I2=16.7%).But,to our disappointment,we still fail to find an effect of rs2718058 on LOAD in the Chinese(OR=1.05,95%CI=0.93~1.17)with evident analysis heterogeneity(I2=57.4%).Conclusions To sum up,our study demonstrated that the rs2718058 loci near gene NME8 on chromosome 7p14.1 might not play a major role in the genetic predisposition to LOAD in the North Han Chinese population. |
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