Association study of the CD۳۳ rs۳۸۶۵۴۴۴ polymorphism in Alzheimer's disease (AD) in the Northern Iranian population

Background and Aim: Alzheimer’s disease (AD) is a complex genetic disorder characterized by the accumulation of amyloid plaques and neurofibrillary tangles (NFTs). Recent genome-wide association studies have identified single nucleotide polymorphism rs۳۸۶۵۴۴۴ in the CD۳۳ gene associated with late-onset AD (LOAD) susceptibility. CD۳۳, also known as Siglec-۳, is a member of sialic acid-binding immunoglobulin-like lectins (Siglecs) family expressed on the surface of myeloid progenitor cells, mature monocytes and macrophages. Considering that conflicting results have been reported on the role of CD۳۳ rs۳۸۶۵۴۴۴ polymorphism in LOAD in different populations, our aim in this study was to investigate the relationship between rs۳۸۶۵۴۴۴ (C) polymorphism and LOAD patients in the North Iranian population.Methods: We carried out a case-control association study to test for a relationship between the rs۳۸۶۵۴۴۴ (C) polymorphism and Alzheimer’s disease in ۱۰۴ patients with LOAD and ۱۰۴ control subjects. The genomic DNA and total RNA were extracted from peripheral blood white cells using the Triton X-۱۰۰ method and TRIzol reagent (Invitrogen, USA), respectively. Genotypes and allele frequencies were determined in two group using Multiplex ARMS-PCR. Real-time quantitative PCR (RT- qPCR) was used to investigate the expression of the CD۳۳ gene at transcription levels.Results: The distribution of genotype and allele frequencies of rs۳۸۶۵۴۴۴ polymorphism was no statistically different between LOAD patients and control group (p=۰.۲۷ and p=۰.۰۸, respectively) while the expression levels of CD۳۳ in peripheral white blood cell were increased in LOAD patients compared to that of control group (P< ۰.۰۵).Conclusion: Results from the case-control study revealed no significant difference between rs۳۸۶۵۴۴۴polymorphism of the CD۳۳ gene and patients with LOAD. However, CD۳۳ gene transcript expression was increased in LOAD patients compared to controls.

Keywords:

CD۳۳ , polymorphism , Alzheimers disease , Immune system , Gene expression