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Background and objective  : Neuroinflammation is one of the pathological pathways of Alzheimer's disease (AD), mediating the progression of neurodegeneration. Polymorphisms of proinflammatory cytokines have been linked to increased AD risk. Identification of certain combinations of polymorphisms could help predict disease in its preclinical stage. The aim of the study was to evaluate differences in the prevalence of TNF α -850T (rs1799724), IL1A -889T (rs1800587), and IL6 -174C (rs1800795, Intron type) polymorphisms between AD patients and healthy controls (HC) and determine the impact of these SNPs in combination with the APOEε4 allele on AD risk. Materials and Methods: The study population is comprised of 107 patients with sporadic AD (AD group) and age- and gender-matched 110 persons without impaired cognitive functions (control group). TNF α -850C &gt; T polymorphism was revealed by a PCR and restriction fragment length polymorphism (RFLP) method. Real time PCR was used for IL1A and IL6 SNP genotyping. APOEε genotyping was done via hybridization method. Results: The frequencies of TNF α -850T, IL1A -889T, IL6 -174C allele and genotype did not differ between the AD and HC groups ( p &gt; 0.05). IL6 -174C was not in HWE, and it was not analysed further. APOEε4 allele ( p = 0.001) and 3/4 and 4/4 genotypes ( p = 0.005) were more prevalent in AD patients. APOEε4 carriage increased the risk of AD (OR 2.65, p = 0.001), while TNF α -850T and IL1A -889T polymorphisms were not found as significant independent risk factors for AD. The presence of at least one IL1A -889T allele in combination with APOEε4+ was associated with a lower risk of AD (OR 2.24, p = 0.047) than the carriage of APOEε4+ alone (OR 2.70, p = 0.015). Conclusions: No significant differences of TNFα -850, IL1A -889, and IL6 -174 polymorphisms frequencies were found between AD and control groups. In APOEε4 carriers IL1A -889T polymorphism was found to reduce the AD risk determined by APOEε4 alone.

Polymorphisms of Proinflammatory Cytokines in Relation to APOE Epsilon 4 and Risk of Alzheimer’s Disease in the Lithuanian Population