Effects of glutathione S-transferase M1 and T1 deletions on Parkinson's disease risk among a North African population

Rebai, Amal; Chbili, Chahra; Amor, Sana Ben; Hassine, A.; Ammou, S. Ben; Saguem, Saâd

doi:10.1016/j.neurol.2020.03.013

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…The outcome of interest with the highest number of studies was the genetics of PD in Africa with 67 articles . Clinical characteristics/features were described in 65 , 14 reported epidemiology 14,[157][158][159][160][161][162][163][164][165][166][167][168][169] , 16 studies investigated environmental risk factors of PD 81,[170][171][172][173][174][175][176][177][178][179][180][181][182] , and 10 studies examined patient experiences and quality of life (QoL) [183][184][185][186][187][188][189][190][191][192] . Studies which examined management and access to care (6) 20,[193][194][195][196][197] and education and training (3) [198][199][200] wer...…”

Section: Resultsmentioning

confidence: 99%

“…These studies focused on three major categories of environmental risk factors including exposure to heavy metals, infections/comorbidities and gene-environment interaction. Three studies (from Tunisia and Egypt) investigated gene-environment interaction among Africans with PD, 81,174,177 four studies (from South Africa, Morocco and Nigeria) investigated exposure to pesticides, heavy metals (manganese ) 175,176,178 , and similar trace elements 172 . These studies showed a positive association of these risk factors in the development of PD, but most were small studies with plans for future large-scale studies.…”

Section: Environmental Risk Factors For Pdmentioning

confidence: 99%

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The State of Play of Parkinson’s Disease in Africa: A Systematic Review and Point of View

Okunoye

Zewde

Azar

et al. 2023

Preprint

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Background: Parkinson's disease (PD) has become a global public health challenge as disability and death due to the disease are growing rapidly in comparison to other neurological disorders. There are no up-to-date comprehensive reviews on the epidemiology, environmental and genetic risk factors, phenotypic characterization, and patient-reported outcomes of PD in Africa. This data is crucial to understanding the current and future burden and suggesting actionable and/or researchable gaps aimed at improving disease outcomes. Methodology: We conducted a systematic literature search using the electronic databases of Cochrane Central Register of Controlled Trials (CCRT), EMBASE, Medline, PsychINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), African Journals (AJOL) and other unpublished literature. We included all studies providing data on people with PD in Africa from the start of each database till February 2023. Studies were not restricted based on diagnostic criteria or language. Outcomes of interest were summarised based on epidemiology, genetics, environmental risk factors, clinical characteristics, patient-reported outcomes (experience and quality of life), disease management and outcomes, access to care, patient support, and healthcare workforce training. We also investigated collaboration between African countries (internal) and across continents/world regions (external) and journal impact factors. Results: A total of 4,855 articles were identified, of which 180 were included in this review. The majority were published from North Africa (mainly from Tunisia, and involved collaboration with investigators from France, the United Kingdom, and the United States of America). West Africa (Nigeria), Southern Africa (South Africa) and East Africa (mainly Tanzania) also had a relatively high number of publications. Methodological design varied across studies. Based on the pre-determined outcomes, articles identified were genetics (67), clinical features (65), environmental risk factors (16), epidemiology (14), patient experience and quality of life (10), management and access to care (5) and education and training (3). Conclusions: The main hubs of PD-related research output in Africa are the Northern, Western and Southern regions of Africa (although with limited involvement of countries within these regions). External collaboration (outside the continent) currently predominates. There are considerable actionable and researchable gaps across all outcomes of interest, with a dearth of published information on health workforce capacity building, disease management and access to care, patient and caregiver engagement, and quality of life of people with PD in Africa. We recommend strengthening existing and emerging intercontinental networks for research, education, training and policy formulation and funding, leveraging on more recent developments such as the International Parkinson's Disease Genomics Consortium-Africa (IPDGC-Africa), the International Parkinson and Movement Disorder Society Africa Section (MDS-AS), World Health Organisation (WHO) and initiatives with similar objectives.

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Section: Resultsmentioning

confidence: 99%

Section: Environmental Risk Factors For Pdmentioning

confidence: 99%

The State of Play of Parkinson’s Disease in Africa: A Systematic Review and Point of View

Okunoye

Zewde

Azar

et al. 2023

Preprint

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“…A number of ESPs such as GSTs, ES-62 and OvS1/Ov20 are implicated in eicosanoid metabolism as well as with its precursor, arachidonic acid and filarial parasite may produce their own eicosanoids. Alterations in the GSTs genes have already been implicated in Alzheimer’s and Parkinson’s disease ( Schmuck et al., 2005 ; Rebai et al., 2021 ).…”

Section: Resultsmentioning

confidence: 99%

The Secretome of Filarial Nematodes and Its Role in Host-Parasite Interactions and Pathogenicity in Onchocerciasis-Associated Epilepsy

Hotterbeekx

Perneel

Vieri

et al. 2021

Front. Cell. Infect. Microbiol.

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Filarial nematodes secrete bioactive molecules which are of interest as potential mediators for manipulating host biology, as they are readily available at the host-parasite interface. The adult parasites can survive for years in the mammalian host, due to their successful modulation of the host immune system and most of these immunomodulatory strategies are based on soluble mediators excreted by the parasite. The secretome of filarial nematodes is a key player in both infection and pathology, making them an interesting target for further investigation. This review summarises the current knowledge regarding the components of the excretory-secretory products (ESPs) of filarial parasites and their bioactive functions in the human host. In addition, the pathogenic potential of the identified components, which are mostly proteins, in the pathophysiology of onchocerciasis-associated epilepsy is discussed.

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“…In Tunisia, neurological diseases are frequent in Tunisia and CNVs could be a risk factor for their expression 38 , 57 . In Center Tunisia, where the prevalence of Parkinson disease is 22/100,000, the GSTM1 null genotype increases the disease risk (OR = 5.45, 95% IC 2.90–10.30, p-value = 10 −6 ) that could be amplified by the presence of the GSTT1 null genotype 58 . Furthermore, Tunisian individuals harboring a homozygous GSTM1 gene deletion exhibit a 3.8 fold increased risk of developing epilepsy (OR = 3.8, 95% IC 2.15–4.78.30, p-value < 10 −6 ) 59 .…”

Section: Discussionmentioning

confidence: 99%

Ethnic and functional differentiation of copy number polymorphisms in Tunisian and HapMap population unveils insights on genome organizational plasticity

Romdhane,

Kefi,

Mezzi

et al. 2024

Sci Rep

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Admixture mapping has been useful in identifying genetic variations linked to phenotypes, adaptation and diseases. Copy number variations (CNVs) represents genomic structural variants spanning large regions of chromosomes reaching several megabases. In this investigation, the “Canary” algorithm was applied to 102 Tunisian samples and 991 individuals from eleven HapMap III populations to genotype 1279 copy number polymorphisms (CNPs). In this present work, we investigate the Tunisian population structure using the CNP makers previously identified among Tunisian. The study revealed that Sub-Saharan African populations exhibited the highest diversity with the highest proportions of allelic CNPs. Among all the African populations, Tunisia showed the least diversity. Individual ancestry proportions computed using STRUCTURE analysis revealed a major European component among Tunisians with lesser contribution from Sub-Saharan Africa and Asia. Population structure analysis indicated the genetic proximity with Europeans and noticeable distance from the Sub-Saharan African and East Asian clusters. Seven genes harbouring Tunisian high-frequent CNPs were identified known to be associated with 9 Mendelian diseases and/or phenotypes. Functional annotation of genes under selection highlighted a noteworthy enrichment of biological processes to receptor pathway and activity as well as glutathione metabolism. Additionally, pathways of potential concern for health such as drug metabolism, infectious diseases and cancers exhibited significant enrichment. The distinctive genetic makeup of the Tunisians might have been influenced by various factors including natural selection and genetic drift, resulting in the development of distinct genetic variations playing roles in specific biological processes. Our research provides a justification for focusing on the exclusive genome organization of this population and uncovers previously overlooked elements of the genome.

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Effects of glutathione S-transferase M1 and T1 deletions on Parkinson's disease risk among a North African population

Cited by 9 publications

References 33 publications

The State of Play of Parkinson’s Disease in Africa: A Systematic Review and Point of View

The State of Play of Parkinson’s Disease in Africa: A Systematic Review and Point of View

The Secretome of Filarial Nematodes and Its Role in Host-Parasite Interactions and Pathogenicity in Onchocerciasis-Associated Epilepsy

Ethnic and functional differentiation of copy number polymorphisms in Tunisian and HapMap population unveils insights on genome organizational plasticity

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