Association of Alzheimer’s Disease with Genetic Variants of Apolipopro-tein 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.
Methods: A total of 42 Saudi AD patients and 23 age-matched control participants were geno-typed 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. Se-rum 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=0.024, OR = 4.00, 95% CI (1.20-13.28)]. For the ApoE SNP rs7412, 40.4% of patients car-ried 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 fre-quency 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 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.
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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…