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. OBJECTIVE To investigate the association of Single Nucleotide Polymorphisms (SNPs) in apolipoprotein E (ApoE), clusterin (CLU), tumor necrotic factor- α (TNF-α) and interleukin-6 (IL-6) genes, with risk of Alzheimer's disease (AD) in Saudi Arabian participants. METHOD 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-α) and rs1800796, rs1800795(IL-6), by RT-PCR using the TaqMan assay. Serum concentrations of amyloid beta peptide 1-40(Aβ1-40), amyloid beta peptide 1-42(Aβ1-42), 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=0.036, OR = 3.67, 95% CI (1.10-12.32)]. For rs429358 (ApoE), patients showed a significantly increased frequency of the TC genotype than controls [p = 0.008, OR = 17.5, 95% CI (2.10-145.78)]. AD patients with CC genotype for ApoE rs429358 had significantly lower levels of Aβ1-40 (p=0.04) in AD patients than controls. Carriers of genotype GG for rs1800629(TNF-α) 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.