Mitochondrial DNA polymorphisms and risk of Parkinson's disease in Spanish population

Huerta, Cecilia; Castro, Marisa; Coto, Eliécer; Blázquez, Marta; Ribacoba, René; Guisasola, Luis M.; Salvador, Carlos; Martı́nez, Carmen; Lahoz, Carlos H.; Álvarez, Victoria

doi:10.1016/j.jns.2005.04.016

Cited by 89 publications

(65 citation statements)

References 36 publications

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“…This was also true for mtSNPs within the COI or cytochrome c oxidase I (C7028T) and COII (G8251A) of complex IV as well as for ATP6 (G9055A) of ATP synthase (for some complex V). Moreover, our data showing a trend for a higher frequency of 9055A (within the ATP6 gene) in female PD patients than in female controls is not in agreement with a protective effect as previously suggested (van der Walt et al 2003;Huerta et al 2005). However, we observed a trend for a decreased PD risk regarding 13708A allele (within the ND5 subunit) in individuals older than 70 years following the stratification of the dataset by age, in accordance with the data from van der Walt et al (2003).…”

Section: Discussioncontrasting

confidence: 81%

Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

et al. 2008

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Mitochondrial complex I deficiency has been implicated in the pathogenesis of Parkinson's disease (PD), but as yet no mitochondrial DNA (mtDNA) variations have been identified that could account for the impaired complex I activity. On the other hand, it has been suggested that mtDNA polymorphisms (mtSNPs) or haplogroups may modify the risk of developing PD. Here, we determined the distributions of ten mtSNPs that define the nine major European haplogroups among 224 PD patients and 383 controls from Crete, an island of 0.6 million inhabitants who share a similar genetic background and a common environment. The recruitment of patients and controls was restricted to individuals of Cretan origin for at least three generations from both parental sides in order to avoid population admixture and subsequent genetic heterogeneity. We found no mtSNP or mtDNA haplogroup that predisposes to PD, although there was a trend for haplogroups J, T, U and I and the supercluster of haplogroups UKJT to be slightly underrepresented in our PD patients as compared to controls. While a combination of common mtSNPs (present in C5% of the general population) may decrease the chance of developing PD, this effect was minor in the Cretan population.

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Section: Discussioncontrasting

confidence: 81%

Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

et al. 2008

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“…As a final QC metric to remove the effects of phylogenetic heterogeneity, nonEuropean samples (i.e., non-HVJTUKWXI and O haplogroups) were removed from subsequent analysis (discovery: cases 5 6 and controls 5 5; replication: cases 5 25 and controls 5 4). Subsequent statistical analysis was based on finalized discovery (PD1 5 [7][8][9][10][11][12][13][14][15] was conducted using Comprehensive Meta-Analysis (version 2, www.meta-analysis.com). 22 In total, 9 published studies (total cases 5 3,030 and total controls 5 4,862) were combined with our larger dataset (discovery: cases 5 1,719 and controls 5 2,889; replication: cases 5 851 and controls 5 2,717).…”

Section: Methodsmentioning

confidence: 99%

Two-stage association study and meta-analysis of mitochondrial DNA variants in Parkinson disease

et al. 2013

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Objectives: Previous associations between mitochondrial DNA (mtDNA) and idiopathic Parkinson disease (PD) have been inconsistent and contradictory. Our aim was to resolve these inconsistencies and determine whether mtDNA has a significant role in the risk of developing PD.Methods: Two-stage genetic association study of 138 common mtDNA variants in 3,074 PD cases and 5,659 ethnically matched controls followed by meta-analysis of 6,140 PD cases and 13,280 controls.Results: In the association study, m.2158T.C and m.11251A.G were associated with a reduced risk of PD in both the discovery and replication cohorts. None of the common European mtDNA haplogroups were consistently associated with PD, but pooling of discovery and replication cohorts revealed a protective association with "super-haplogroup" JT. In the meta-analysis, there was a reduced risk of PD with haplogroups J, K, and T and super-haplogroup JT, and an increase in the risk of PD with super-haplogroup H. Conclusions:In a 2-stage association study of mtDNA variants and PD, we confirm the reduced risk of PD with super-haplogroup JT and resolve this at the J1b level. Meta-analysis explains the previous inconsistent associations that likely arise through sampling effects. The reduced risk of PD with haplogroups J, K, and T is mirrored by an increased risk of PD in super-haplogroup HV, which increases survival after sepsis. Antagonistic pleiotropy between mtDNA haplogroups may thus be shaping the genetic landscape in humans, leading to an increased risk of PD in later life. Multiple lines of evidence implicate mitochondria in the pathogenesis of idiopathic Parkinson disease (PD). A defect of respiratory chain complex I has been documented in the substantia nigra of postmortem PD brains, 1 and the potent complex I inhibitor MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) causes parkinsonism and nigrostriatal dopaminergic degeneration in humans.2 Exposing rats to the complex I inhibitor rotenone causes tremor and rigidity with associated loss of substantia nigra neurons and aggregation of a-synuclein, a major constituent of Lewy bodies, which characterize the neuropathology of PD.3 Furthermore, several monogenic forms of PD are due to mutations in genes coding for mitochondrial proteins or mitochondrial maintenance/autophagy (including PARK2, 4 PINK1, 5 and DJ 5), which compromise oxidative phosphorylation.Mitochondrial DNA (mtDNA) codes for 13 respiratory chain proteins that are essential for the synthesis of the intracellular energy source adenosine triphosphate. Point mutations of mtDNA compromise oxidative phosphorylation and cause severe multisystem neurologic disorders with

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“…233,235 Whereas this mutation has been presented as a polymorphism, 237 has a significantly increased frequency in PD patients compared to controls. 238 However Simon et al 239 were unable to confirm the association between A4336G mutation and Parkinson disease. Two other point mutations G15950A in tRNA Thr and T15965C in tRNA Pro have been detected in PD patients.…”

Section: The Clinical Phenotypes Of Mitochondrial Trna Mutationsmentioning

confidence: 99%

Mitochondrial tRNA Mutations: Clinical and Functional Perturbations

Zifa

Giannouli²,

Theotokis³

et al. 2007

RNA Biology

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Mitochondrial DNA polymorphisms and risk of Parkinson's disease in Spanish population

Cited by 89 publications

References 36 publications

Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

Two-stage association study and meta-analysis of mitochondrial DNA variants in Parkinson disease

Mitochondrial tRNA Mutations: Clinical and Functional Perturbations

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