Clusterin, TNF-α, and IL-6 polymorphism and implications on Alzheimer’s disease risk determination in Saudi population

Abstract Background: In the wake of the warning by WHO that the prevalence of dementia may rise by 125% in Middle East by 2050, identification of genetic risk factors in Arab population is urgent.Methods: To genotype the Single Nucleotide Polymorphisms (SNPs) in clusterin (CLU) rs11136000, rs1532278; tumor necrotic factor (TNF-α) -308 rs1800629 A/G and -857 rs1799724 T/C; interleukin-6 (IL-6) rs1800796 G/C (-572 G/C) and rs1800795 G/C (-174 G/C), and to determine their association with Alzeimer’s Disease (AD), DNA was isolated from the blood of 42 elderly Saudi AD patients (19 male, 23 female) and 23 healthy controls (11 male, 12 female), recruited for this study. Total serum cholesterol, LDL-C, HDL-C, and triglyceride levels were measured using an autoanalyzer. Serum concentrations of beta-amyloid 1–40 (Aβ1-40), beta-amyloid 1–42 (Aβ1-42), CLU, and inflammatory biomarkers (IL-6, TNF-α, and the C-reactive protein) were assessed by ELISA. The gene polymorphisms were analyzed by RT-PCR using the TaqMan assay. Results: The results show that in the rs1532278 SNP of CLU gene, GA heterozygous allele was significantly higher in AD patients (57.1%) than in the control subjects (26.1%; OR = 3.67, CI = 1.10-12.32; p=0.036), thus it may be a risk factor for AD. On the other hand, the AD patients who carried genotype GG for TNF-α SNP rs1800629 showed significantly higher levels of serum IL-6 (p = 0.04), and hence may increase susceptibility to AD in Saudi population.