Mitochondrial DNA and Alzheimer's disease: a first case-control study of the Tunisian population.

Nesrine Ben Salem,Amel Ben Ammar Elgaaied,Samia Younes,Imene Mahmoud,Afef Hammami,Agustín Ruiz,Mahbouba Frih-Ayed,Lotfi Cherni,Narjes Mokni,Itziar De Rojas,Nizar Daouassi,Sonia Moreno-Grau,Laura Montrreal,Sami Boussetta

doi:10.1007/s11033-021-06978-7

Abstract

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. 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. 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). 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.

Highlights

Alzheimer’s disease (AD; MIM 104300) is the major cause of dementia and the most common neurodegenerative disorder (Bekris et al 2010; Bi et al 2015)
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
We evaluated the possible association between AD and mitochondrial haplogroups or polymorphisms in the Tunisian population by genotyping mitochondrial polymorphisms dispersed across the whole mitochondrial genome, using a cohort of 58 AD patients and 196 controls comparable in gender, age, and ethnicity

Summary

Introduction

Alzheimer’s disease (AD; MIM 104300) is the major cause of dementia and the most common neurodegenerative disorder (Bekris et al 2010; Bi et al 2015). The genetic cause is still not known, especially because patients with the LOAD phenotype show no mutations in presenile genes and amyloid precursor protein (APP) (Fesahat et al 2007; Rezazadeh et al 2019). Besides mutations in the APOE e4 allele, genetic variations in more than 20 susceptibility genes have been identified by genome-wide association studies and next-generation sequencing. These genes are involved in many biological functions, such as immune response, synapse function, and lipid metabolism. Mitochondrial alteration has been proposed as a possible cause of AD several studies have focused on finding an association between inherited mitochondrial DNA variants and AD onset

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