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Background: Alzheimer's disease (Alzheimer! s disease, AD) is a common progressive neurodegenerative disease in the central nervous system, is the main reason to lead to pre-elderly and senile dementia, the clinical manifestations of memory loss, cognitive dysfunction, personality changes and language disorders, neuropsychiatric symptoms characterized. Between 1906 and 1907 by the German neurologist Alois Alzheimer first discovered. Currently, there are around 2000 to 30 million patients with AD. The statistics show that Europe and the United States, 65 years of age or older dementia prevalence rate of 3.0% to 5.0%, more than half of them for AD. AD has become in the United States, the four causes of death after following cardiovascular disease, cancer and stroke. AD incidence of domestic and foreign similar number of cases has reached 100,000. It is reported that the prevalence of dementia was 0.75% -4.69% of people over the age of 60. As the world population is increasingly aging, AD has become one of the most serious issue facing today's geriatrics. The etiology and pathogenesis of AD is not clear so far, it is generally believed that AD is a complex heterogeneous disease, a variety of factors may be involved in pathogenicity, such as genetic factors, neurotransmitters, immune factors, and environmental factors. Therefore, when the body to the existence of certain genetic defects, genetic defects of the key enzymes of the enzyme system such as those related to the metabolism and toxicology, and having a central protective effect of estrogen synthesis, may cause accumulation of toxins in the body, cause chronic damage to the nervous system. The complexity of the process of biotransformation of xenobiotics vivo depends on the combined effect of a variety of enzymes and the activity balance between. Xenobiotics biotransformation in the body rely on metabolic enzyme I enzyme (cytochrome P450) by oxidation, reduction and hydrolysis to change the function of the gene or its chemicals decomposition II phase enzyme (such as glutathione-S-transferase enzyme, catalytic exogenous chemical substances of the N-acetyl transferase) with some strongly polar group (such as methyl, acetyl) binding reaction occurs, so that the polarity or aqueous enhancements, is conducive to the discharge with the urine or bile. The conversion process depends on the complexity of the common role for a variety of metabolic enzymes and their activity balance. Glutathione S-transferase (Glutathione S-transferase, GST) are phase Ⅱ metabolic enzymes, the body is important detoxification enzyme, which catalyzes electrophilic compounds with reduced glutathione binding reaction, the former dysfunction live, have an important role in the metabolism of environmental carcinogens and chemotherapeutic drugs excreted through urine or bile. GSTs is a group of detoxification function of the protein superfamily can be divided into the cytoplasm, or cell membrane, mitochondria and LTC4 synthase. Expression in almost all cells and tissues have the highest expression in the liver, colon and gonads. Has found that GSTM1, P1 has a population polymorphism. GSTs genetic polymorphisms and environmental factors interact to affect human susceptibility to certain diseases. Correct understanding of the relationship GSTs genetic polymorphisms and environmental factors have important significance for revealing the causes of disease, improve the forecast level of patients with disease susceptibility. Glutathione S-transferase P1 (GSTP1) gene exon 5 (Ile105 → Val) polymorphism. GSTP1 gene encoded product GSTP1 enzyme contains 210 amino acids, and studies have shown that the amino acid sequence is located in the first 105-point is very important for the biological function of the protein, the amino acid substitution of the locus change of the volume of amino acids and hydrophobic, which affects the enzyme thermal stability. It is reported that the thermal stability of the GSTP1 enzyme-Val105 than of GSTP1 Enzyme-Ile105 low 2 to 3 times. With the deepening of the the GSTP1 gene structure and function research, it has been recognized that there are significant differences in the GSTP1 alleles encoding the enzyme in the oxidative metabolism. Therefore, the polymorphism of GSTP1 coding genes may be related to the genetic susceptibility of AD. The study found that endogenous estrogen levels in postmenopausal patients with AD same age was significantly lower than the control group of non-AD patients, the local formation of estrogens has obvious neurotrophic and neuroprotective effects. Such as estrogen by promoting neurotrophic factor neurotrophin receptor expression and raised its neurotrophic effects. Conversely, the neurotrophic factor can promote cell in combination with estrogen, cause the signal to enlarge, thereby strengthening the neurotrophic effects. Estrogen treatment of AD (especially in the prevention of) aspects of the role of very exciting, its mechanism of action is becoming a research focus at home and abroad. Aromatase is the last step of the rate-limiting enzyme in estrogen synthesis, is one of the cytochrome P450 superfamily encoding gene CYP19 located 21 District 1, the long arm of chromosome 15, with a total length of 123Kb. The study found that the estrogen synthesis by aromatase is closely related to brain development and regeneration. Under normal circumstances, the distribution of aromatase in a variety of tissues in people and other mammals, such as: central nervous system, placenta syncytiotrophoblast, ovarian granulosa cells, adipose tissue, and stromal cells, adrenal tissue. In specific brain regions, aromatase catalytic androgen into estrogen related cerebral aromatase activity in high and low estrogen levels. In recent years, research has shown that: the CYP19 gene, including many of the tissue-specific promoter mediated CYP19 gene expression and to determine CYP19 gene expression of tissue-specific mode. At home and abroad is less research on the relationship between aromatase AD. CYP19 has a population polymorphism has been found, the CYP19 coding gene polymorphism may be associated with AD genetic susceptibility. Objective: The objective of this study is to investigate the CYP19 gene GSTP1 gene polymorphism with genetic susceptibility to Alzheimer's disease, providing molecular markers for the clinical diagnosis of Alzheimer's disease. Methods: 102 cases of Alzheimer's disease patients blood samples from the Beijing hospital and army retired cadres. The blood samples of the control group from the community healthy elderly subjects (≥ 65 years), MMSE score ≥ 28 points, a total of 121 cases. Dementia diagnosis according to ICD-10 diagnostic criteria for the possibility of AD \All subjects pumping whole blood 2 mL of sodium citrate by phenol chloroform extraction of genomic DNA extracted from peripheral blood. Use of the polymerase chain reaction - restriction fragment length polymorphism, application upstream 5'-TGC TAT CGT GGT TAA AAT CCA AGG-3 'and downstream 5'-TTA CCT GAG AGGCCA AGA AAA ACA-3' primers amplified cells pigment CYP19 gene Mfe Ⅰ sites alleles application Mfe Ⅰ restriction enzyme detected A → T polymorphism; application upstream 5'-ACC CCA GGG CTCTAT GGG AA-3 'and downstream 5'-TGA GGG CAC AAG AAG CCC CT-3 'This primer pair GSTP1 gene, application BsmA Ⅰ restriction enzymes were used to detect the GSTP1 gene A → G polymorphism. Comparative gene frequencies and genotypes using SPSS13.0 statistical package, calculated using the chi-square test between Alzheimer's disease patients with normal allele frequency or mutation frequency. Results: CYP19 gene Mfe I polymorphism with Alzheimer's disease, the relationship between CYP19 gene Mfe Ⅰ A → T polymorphic test results show that the proportion in the Alzheimer's disease group allele m1, m2 were 135/204 (66.2% ) and 69/204 (33.8%) in the control group were 196/242 (81.0%) and 46/242 (19.0%), the two groups have a significant difference (χ to 2 = 12.696, P <0.05 , 95% CI: 1.413 ~ 3.357). The various genotype frequencies of the CYP19 gene Mfe Ⅰ sites: Alzheimer's disease group m1/m1, m1/m2, m2/m2 were 45/102 (44.1%), 45/102 (44.1%), 12/102 (11.8%), while the normal control group were 79/121 (65.3%), 38/121 (31.4%), 4/121 (3.3%), between the case group and the normal control group CYP1A1 gene Msp Ⅰ point various significant difference in genotype distribution (χ ~ 2 = 12.384P <0.05). GSTP1 gene polymorphism and Alzheimer's disease alleles M1, M2 distribution of frequency in the case group were 73.4%, 26.6%; 83.1% in the control group, 16.9%, were statistically two allele frequency distribution of differences between groups was significant (χ ~ 2 = 6.134 P <0.05,95% CI: 1.124 ~ 2.809). The GSTP1 gene BsmA Ⅰ locus genotype frequencies: Alzheimer's disease group m1/m1, m1/m2, m2/m2 were 56/102 (54.9%), 37/102, 9/102 (36.3%) (8.8%), and the normal control group were 85/121 (70.2%), 31/121 (25.6%), 5/121 (4.1%), between the case group and the normal control group CYP1A1 gene Msp Ⅰ point a variety of The genotype distributions significant difference (χ ~ 2 = 6.062P <0.05). Conclusion: this group of normal healthy elderly the CYP19 gene Mfe Ⅰ sites genotype and GSTP1 gene BsmA Ⅰ locus genotypes considerable proportion of reported data the average of the normal population. The study found that (1) the CYP19 gene Mfe Ⅰ locus gene frequencies and genotype distribution of significant differences in the AD group and normal control group, suggesting that carry a mutation in T can increase the incidence of sporadic Alzheimer's disease. (2) the GSTP1 gene BsmA Ⅰ locus gene frequencies and genotype distribution in both groups there is a significant difference, suggesting that prompted carry the mutant gene G can increase the incidence of sporadic Alzheimer's disease.
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