Nesrine Ben Salem1,2, Sami Boussetta3, Itziar de Rojas4,5, Sonia Moreno-Grau4,5, Laura Montrreal4, Narjes Mokni6, Imene Mahmoud6, Samia Younes7, Nizar Daouassi6, Mahbouba Frih-Ayed6, Afef Hammami8, Amel Ben Ammar Elgaaied3, Agustín Ruiz4,5, Lotfi Cherni3,9. 1. Laboratory of Genetics, Immunology and Human Pathology, Faculty of Science of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia. nesrinebensalem@hotmail.com. 2. High Institute of Biotechnology, University of Monastir, Monastir, Tunisia. nesrinebensalem@hotmail.com. 3. Laboratory of Genetics, Immunology and Human Pathology, Faculty of Science of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia. 4. Research Center and Memory Clinic Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain. 5. CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain. 6. Neurological Department Hospital University Center of Monastir, Monastir, Tunisia. 7. Department of Neurology, University Hospital of Mahdia, Mahdia, Tunisia. 8. Alzheimer Family Assistance Center (AFA Center), Tunis, Tunisia. 9. High Institute of Biotechnology, University of Monastir, Monastir, Tunisia.
Abstract
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial alteration has been proposed as a possible cause of AD. Therefore, several studies have focused on finding an association between inherited mitochondrial DNA variants and AD onset. METHODS: In this study, we looked, for the first time, for a potential association between mitochondrial haplogroups or polymorphisms and AD in the Tunisian population. We also evaluated the distribution of the major genetic risk factor for AD, the apolipoprotein E epsilon 4 (APOE ε4), in this population. In total, 159 single-nucleotide polymorphisms (SNPs) of mitochondrial DNA haplogroups were genotyped in 254 individuals (58 patients and 196 controls). An additional genotyping of APOE ε4 was performed. RESULTS: No significant association between mitochondrial haplogroups and AD was found. However, two individual SNPs, A5656G (p = 0.03821, OR = 10.46) and A13759G (p = 0.03719, OR = 10.78), showed a significant association with AD. APOE 4 was confirmed as a risk factor for AD (p = 0.000014). CONCLUSION: Our findings may confirm the absence of a relation between mitochondrial haplogroups and AD and support the possible involvement of some inherited variants in the pathogenicity of AD.
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial alteration has been proposed as a possible cause of AD. Therefore, several studies have focused on finding an association between inherited mitochondrial DNA variants and AD onset. METHODS: In this study, we looked, for the first time, for a potential association between mitochondrial haplogroups or polymorphisms and AD in the Tunisian population. We also evaluated the distribution of the major genetic risk factor for AD, the apolipoprotein E epsilon 4 (APOE ε4), in this population. In total, 159 single-nucleotide polymorphisms (SNPs) of mitochondrial DNA haplogroups were genotyped in 254 individuals (58 patients and 196 controls). An additional genotyping of APOE ε4 was performed. RESULTS: No significant association between mitochondrial haplogroups and AD was found. However, two individual SNPs, A5656G (p = 0.03821, OR = 10.46) and A13759G (p = 0.03719, OR = 10.78), showed a significant association with AD. APOE 4 was confirmed as a risk factor for AD (p = 0.000014). CONCLUSION: Our findings may confirm the absence of a relation between mitochondrial haplogroups and AD and support the possible involvement of some inherited variants in the pathogenicity of AD.
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