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Association of ApoE 、 TNF- α -850C/T Gene Polymorphisms with Alzheimer’s Disease

Author: RaoWeiHua
Tutor: WangYanPing
School: Guangzhou Medical College
Course: Neurology
Keywords: Alzheimer’s disease gene polymorphisms ApoE TNF-α-850
CLC: R749.16
Type: Master's thesis
Year: 2011
Downloads: 33
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Abstract

Backgroud: Alzheimer disease(AD) are common neurodegenerative disorders in the aged. The cause and the pathogenic mechanisms of AD are unclear. In the present study, there is definite link between inflammatory factors and AD. There are many activated microglia aroud the degenerative neuron in animal models and pathologic autopsy. These microglia release many inflammatory factors including TNF-α. These inflammatory factors mainly exist in amyloid protein and senile plaque in AD patients. These researches demonstrate the inflammatory factors that activated microglia release may be attend the course that AD patients’neuron degeneration. Currently,several large-scale studies abroad indicated that the risk of Alzheimer’s disease in those people who carry the apolipoprotein Eε4 allele and TNF-αgene at the position of -850 T allele is higher than in those people who only carry the apolipoprotein Eε4 allele. Whether the incidence of domestic Alzheimer’s disease is associate with TNF-α-850 gene polymorphism? There is no reports related at home. At present, a large number of studies confirm that there is closely relationgship between ApoE gene polymorphism and Alzheimer’s disease. ApoEε4 allele is a risk factor of AD. Whether ApoEε2 is a protective factor of AD?The conclusion at home and abroad is not consistent.Objective:Our study on identification of ApoE gene associated with TNF-α-850 gene was purposed to investigate whether there were ApoE and TNF-α-850 gene polymorphisms or not and the frequencies of genotype and allele in different populations. As well as, our objective of the study was to analyse the association of apolipoprotein E and tumour necrosis factor-α(TNF-α) gene polymorphisms at position -850C/T in Chinese population of Guangdong province with Alzheimer’s disease and to explore the genetic background of AD. We expect that our study will provide the foundation of early diagnosis and early selection of Alzheimer’s disease.Method:We conducted a case--control study. 37 cases AD patients and 72 cases normal controls were enrolled. Genome DNA from the peripheral venous blood was taken respectively. TNF-αgene polymorphisms at position -850C/T were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-PFLP) method. Apply SPSS17.0 statistical analysis software to read alleles and genotypes of individual samples,and each group allele frequencies and genotype compared with chi-square test and logistic regression analysis.The value of P less than 0.05 is considered statistically significant.Result:1. AD group and normal controls were similar in age and sex, subgroups were matehed by age, sex, disease duration.2. The distributions of ApoE and TNF-αgenetypes followed the law of Hardy-Weinberg equilibrium. In either AD group or normal control group , the allele of ApoEε3 was most common and genotype ofε3/3 was most frequently seen in Chinese polulation of Guangzhou province. The ApoEε4 frequency was significantly higher in AD patients than that in the normal controls (P<0.05). The age and sex-adjusted, Odds ratio for the risk of AD in carriers of ApoEε4 allele was 5.333(Odds Ratio=5.333, 95% confidence interval: 2.054-13, 851, P=0.001). The distribution of ApoEε2 allele frequency in AD group and normal group was no significant difference(P<0.05). 3. Our data showed that the distribution of every TNF-α-850 genotype and allele were no significantly different in AD patients compared with normal controls(P>0.05). In addition, associated with the ApoEε4 allele, the distribution of every TNF-α-850 genotype and allele were still no significantly different in AD group compared with normal controls(P>0.05).Conclusion:1. In chinese population of Guangdong province, there is close relationgship between apolipoprotein E gene polymorphisms and Alzheimer’s disease. ApoE geneε4 allele carrier is a risk factor for AD patients while ApoE geneε2 allele carrier is propably not a protective factor for AD patients.2. From the current Number of cases investigated, In chinese population of Guangdong province, there is no directly correlation between TNF-αgene at position -850 polymorphisms and Alzheimer’s disease. TNF-α-850 T allele is probably not a risk factor for Alzheimer’s disease patients. Individuals carrying TNF-α-850 T allele and ApoEε4 allele is not at increased risk in additional for Alzheimer’s disease as compared with those with ApoEε4 allele merely.

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