ABSTRACT
Purpose: 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. Materials and Method: 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). Results: 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). Conclusion: 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.
Acknowledgements
The authors are especially grateful to the Sahloul University Hospital Neurology Department stuff for their efforts and support. They are also grateful to the study participants for their cooperation. They acknowledge the general director of the Sahloul University Hospital and the excellent technical assistance of all of the Biochemistry Department members. This study could not have been undertaken without their extremely generous and strong support.
Disclosure statement
No potential conflict of interest was reported by the authors.
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Notes on contributors
Hamdouni Haithem
Hamdouni Haithem is a Ph.D student.
Achour Ons
Achour Ons is a Ph.D student.
Naija Salma
Naija Salma, M.D., is a neurology medical doctor at Neurology Department, Sahloul University Hospital, Sousse, Tunisia, and a professor assistant at the Faculty of Medicine, Sousse, Tunisia.
Rejeb Jihène
Rejeb Jihene is a Ph.D in molecular and cellular Biology.
Aounallah Mariam
Aounallah Mariam is a doctor of Pharmacy (Pharm.D.).
Mhiri Mariem
Mhiri Mariem is a neurology resident medical officer at Neurology Department, Sahloul University Hospital, Sousse, Tunisia.
Noureddine Mariem
Noureddine Mariem is a doctor of Pharmacy (Pharm.D.).
Ben Rejeb Nabila
Ben Rejeb Nabila is a university hospital professor at Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia; and a biochemistry professor at the Faculty of Pharmacy, Monastir, Tunisia.
Omezzine Asma
Omezzine Asma, Ph.D, is a university hospital professor at Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia, and Biochemistry professor at the Faculty of Pharmacy, Monastir, Tunisia.
Ben Amor Sana
Ben Amor Sana is a neurology medical doctor at Neurology Department, Sahloul University Hospital , Sousse, Tunisia, and a professor of Medicine at the Faculty of Medicine, Sousse, Tunisia.
Benammou Sofien
Benammou Sofien is a neurology medical doctor at Neurology Department, Sahloul University Hospital , Sousse, Tunisia, a professor of Medicine at the Faculty of Medicine, Sousse, Tunisia, and a head of the Neurology Department, Sahloul University Hospital, Sousse, Tunisia.
Bouslama Ali
Bouslama Ali is a university hospital professor at Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia, biochemistry professor at the Faculty of Pharmacy, Monastir, Tunisia, a head of the Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia, and a director of the Research Laboratory LR12SP11.