GENETIC VARIANTS OF CLU (RS9331896) AND BIN1 (RS6733839) IN ALZHEIMER’S DISEASE: PATIENTS CARRIERS AND NON-CARRIERS OF APOE4 ALLELE

Abstract

Currently, Alzheimer disease (AD) risk polymorphisms include among others APOE, TOMM40, CLU, and BIN1genes. APOE possess 3 alleles: protective (E2), neutral (E3) and pathogenic (E4). Similar to APOE, the clusterin (CLU) gene also known as apolipoprotein J is present in amyloid plaques and binds to Aβ peptides. Moreover, the CLU gene plays an important role in lipid transport, apoptosis, immune system, and neurogenesis. BIN1 gene is also involved in the regulation of apoptosis and immune response. It is also implicated in synaptic vesicle endocytosis, intracellular APP trafficking. APOE, CLU, and BIN1 are associated with late-onset AD (LOAD) risk. So far, the correlation between these genes has not been studied in the Polish population. The aim of the study was to analyze the CLU and BIN1 polymorphisms in carriers and non-carriers of APOE4 allele: AD patients and related (CR), and unrelated (CU) controls with AD patients. The studies were conducted on 40 patients with AD. The control group included 47 CR and 39 CU. The APOE genotype was determined by real-time PCR. The CLU and BIN1 genotypes were determined by HRM and sequencing. The study showed that incorrect CLU TT homozygous genotype occurred with the same frequency in CR and CU, and 3-times less often than in AD patients. However, incorrect BIN1 TT homozygous genotype occurred 5-times less often in CU than in CR and AD. At the same time, in the non-carriers of APOE4 allele: CLU TT occurred only in CU and AD, and in AD patients appear 2-times more often than in CU and BIN1 TT occurred 3-times less often in CU, AD than in CR. In the carriers of APOE4 allele: CLU TT occurred with the same frequency in CR and AD, and in AD patients appear 3-times more often than in CU. However, BIN1 TT occurred only in CR and AD, and in AD patients appear 2-times more often than in CR. It seems that AD is a complex neurodegenerative disease with a strong genetic component such as APOE, CLU and BIN1.