بررسی ارتباط واریاسیون‌های ژن‌های APOE و TNF-α با بیماری آلزایمر اسپورادیک در جمعیت ایرانی

Objectives: Several studies indicate that amyloid ß (Aß) peptide deposits and neurofibrillary tangles have key roles in pathogenesis and progression of the late-onset Alzhimer’s disease. Likewise it has been shown that inflammatory reactions play a significant role as well. Inflammatory mediators such as complement, chemokines and cytokines activators and inhibitors can release from activated microglia and astrocytes, causing neuronal dysfunction and death. One of the most important cytokines is tumor necrosis factor–α (TNF-α). This study was designed and carried out to determine the association between sporadic Alzheimer’s disease and the human TNF-α and APOE gene variations in Iranian population. Methods & Materials: In this case-control study, the role of TNF-α gene polymorphism was determined in 167 sporadic AD patients and 163 healthy controls. Genomic DNA was extracted using standard salting out method from peripheral lymphocytes and TNF-α- 850C/T promoter polymorphism was genotyped using PCR/RFLP technique. Comparing the genotype and allelic frequencies were analyzed using chi-square and logistic regression tests by SPSS 11.5. Results: The obtained results indicated that the frequency of TNF-α -850 heterozygote genotype (CT) was significantly higher in AD patients comparing healthy controls (P=0.038). Although no significant difference were observed in TNF-α -850 homozygote genotype (TT) and T allele between the studied groups. No interaction was shown between TNF-α -850 and APOE gene polymorphisms as well. Conclusion: These data suggests the role of TNF-α -850 TC genotype as a risk factor for AD in Iranian population. Although to show the effects of homozygote genotype (TT) and T allele, a study with a larger sample size maybe indicated.