Association between dementia and vascular disease-associated polymorphisms in a Tunisian population

Dementia is a multifactorial idiopathic pathology caused by clinical, eDementia is a multifactorial idiopathic pathology caused by clinical, environmental and genetic factors. Hence, its etiology is still unknown. We aimed to evaluate the association between five genetic risk factors for vascular diseases and dementia individually and when gathered in haplotypes.

We enrolled 200 dementia patients and 300 controls. All subjects were genotyped for vascular diseaseassociated polymorphisms in the genes coding for Apolipoprotein-E (ApoE), angiotensin converting enzyme (ACE) and Paraoxonase-1 (PON1).

The association between dementia risk and all the studied polymorphisms except of PON1-Q192R was found to be significant. Carrying the ApoE e4 allele seems to increase dementia risk by 4.32 fold (p = 0.001). The risk associated with ACE I and PON1-L55M T alleles were lower (2.58 and 2.11 fold, p < 0.001 and p = 0.015, respectively). When combined in haplotypes, these polymorphisms showed a cumulative and synergetic effect. GTICC haplotype appears to be associated with 9-fold dementia risk (p < 0.001), whereas AADTT seems to reduce dementia risk by 80% (p = 0.003).

Our results suggest that, ApoE ε4, ACE I and PON1-L55M T alleles are associated with dementia risk whether these polymorphisms were studied separately or gathered in haplotypes. Still, the contribution of each gene to the pathophysiological development of dementia must be more investigated.