Genetic association study between rs2234253 (p.T96K) variant of TREM2 and Alzheimer's disease in a Tunisian population.

Abstract

Background: Alzheimer's disease (AD) is the leading cause of major neurodegenerative cognitive impairment. The risk of developing AD is influenced by a complex interaction of genetic predisposition and environmental factors. Among the genetic risk factors, the APOE ɛ4 allele is the most significant, while variants in the TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) and ABCA7 (ATP-binding cassette transporter A7) genes have also been associated with an increased risk of AD.

Objective: This study aimed to investigate the association of APOE ɛ4, TREM2 gene variants (rs75932628 [p.R47H] and rs2234253 [p.T96K]), and ABCA7 gene variants (rs142076058 and rs115550680) with sporadic AD in the Tunisian population. Methods: A case-control study was conducted including 222 Tunisian patients diagnosed with sporadic AD and 99 cognitively healthy controls. Genotyping was performed to assess the presence and association of the selected genetic variants with AD. Statistical analyses were conducted to determine the significance of genetic associations.

Results: A significant association was found between the TREM2 rs2234253 (p.T96K) variant and AD, with the T allele identified as a risk factor in the Tunisian population. The APOE ɛ4 allele was also associated with an increased risk of developing AD. However, no significant association was observed for the ABCA7 gene variants or the TREM2 rs75932628 (p.R47H) variant in either the AD or control groups.

Conclusion: Our findings suggest that the TREM2 rs2234253 (p.T96K) variant is a significant genetic risk factor for late-onset AD (LOAD) in the Tunisian population. Further studies with larger cohorts are needed to validate these findings and explore potential gene-gene interactions contributing to AD risk.