Studija povezanosti varijante R47H gena TREM2 sa genetičkom podložnošću za Alchajmerovu bolest u populaciji Srbije

Abstract

Introduction: Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is clinically manifested by the development of dementia. Studies of genetic susceptibility to AD indicate a whole range of genes and their variants that can potentially influence an individual's susceptibility to develope the disease. AD17 represents a form of Alzheimer's disease associated with mutation(s) in the TREM2 gene, encoding triggering receptor expressed on myeloid cells 2. The aim of this study was to determine the frequency of R47H variant of the TREM2 gene in the population of AD patients, to compare the frequency of the variant in the population of AD patients and the control group, and to determine a possible association of a certain genotype with susceptibility to AD. Material and Methods: The study included 168 consecutive patients with AD and 190 healthy controls. The clinical inerview, neurologic examination, and neuropsychological set of cognitive assessment were performed by neurologists and neuropsychologists in expertise with neurodegenerative deseases. Genotyping of rs75932628, R47H polymorphism of the TREM2 gene was performed using Real-time Polymerase Chain Reaction and TaqMan® SNP genotyping assay (Applied Biosystem by Thermo Fisher Scientific, USA) according to the manufacturer's recommendations. Results: In the group of AD patients the frequency of C allele was 98.8%, while the T allele was present in 1.2% of patients. The frequency of the T allele was statistically significantly higher among the AD population than among the control group (p<0.05). The frequency of homozygotes without mutation (CC genotype) was 97.62%, while the frequency of heterozygotes for the mutation (CT genotype) was 2.38% among patients with AD, and the frequency of homozygotes without mutation (CC genotype) was 100% among healthy controls. Conclusion: Our study indicated a possible association of the heterozygous form of the R47H variant of TREM2 gene with the susceptibility for the deve-lopement of AD in Serbian population.