Association of Alzheimer's Disease with Genetic Variants of Apolipoprotein E, Clusterin, TNF-α, and IL-6 Among Elderly Saudis

Background: In the wake of the warning by WHO that the prevalence of dementia may have a rise of 125% in the Middle East by 2050, identification of the genetic risk factors in Arab populations is urgent. Objectives: To investigate the association of Single Nucleotide Polymorphisms (SNPs) in apolipoprotein E (ApoE), clusterin (CLU), tumor necrotic factor-alpha (TNF-alpha) and interleukin-6 (IL-6) genes, with risk of Alzheimer's disease (AD) in Saudi Arabian participants. Methods: A total of 42 Saudi AD patients and 23 age-matched control participants were genotyped for eight SNPs: rs429358, rs7412 (ApoE); rs11136000, rs1532278 (CLU); rs1800629, rs1799724 (TNF-alpha) and rs1800796, rs1800795(IL-6), by RT-PCR using the TaqMan assay. Serum concentrations of amyloid beta peptide 1-40(A beta 1-40), amyloid beta peptide 1-42(A beta 1-42), CLU and some other biochemical markers were measured. Results: A significant increase (p=0.004) in the serum CLU level was detected in the AD group (340.4 +/- 74.6) compared with control group (265.0 +/- 80.9). For rs1532278 (CLU), genotype GA was significantly higher in AD patients (57.1%) than in the control participants (26.1%), [p=0.024, OR = 4.00, 95% CI (1.20-13.28)]. For the ApoE SNP rs7412, 40.4% of patients carried a TT genotype, whereas it was completely absent in the controls [p = 0.020, OR = 30.53, 95% CI (1.73 - 540.05)]. For rs429358 (ApoE), patients showed a significantly increased frequency of the TC genotype [p = 0.006, OR = 9.33, 95% CI (1.89-46.19)] and TT [p = 0.045, OR = 19.76, 95% CI (1.07-366.0)] genotype than controls. AD patients with CC genotype for ApoE rs429358 had significantly lower levels of A beta 1-40 (p=0.04) in AD patients than controls. Carriers of genotype GG for rs1800629 (TNF-alpha) showed significantly higher levels of serum IL-6 (p = 0.04) in AD patients. Conclusion: Genetic variants in ApoE and CLU may influence susceptibility to AD among Saudi Arabian participants.