Mitochondrial DNA polymorphisms and risk of Parkinson's disease in Spanish population (original) (raw)
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Journal of Human Genetics, 2008
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.
Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson's disease in Italians
European Journal of Human Genetics, 2005
It has been proposed that European mitochondrial DNA (mtDNA) haplogroups J and K, and their shared 10398G single-nucleotide polymorphism (SNP) in the ND3 gene, are protective from Parkinson's disease (PD). We evaluated the distribution of the different mtDNA haplogroups in a large cohort of 620 Italian patients with adult-onset (450, o65 years of age) idiopathic PD vs two groups of ethnic-matched controls. Neither the frequencies of haplogroup J nor that of 10398G were significantly different. However, the frequency of haplogroup K was significantly lower in PD. Stratification by sex and age indicated that the difference in the distribution of haplogroup K was more prominent in 450year old males. In spite of the common 10398G SNP, haplogroups J and K belong to widely diverging mitochondrial clades, a consideration that may explain the different results obtained for the two haplogroups in our cohorts. Our study suggests that haplogroup K might confer a lower risk for PD in Italians, corroborating the idea that the mitochondrial oxidative phosphorylation pathway is involved in the susceptibility to idiopathic PD.
Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese
Chinese medical journal, 2015
Mitochondrial dysfunction is linked to the pathogenesis of Parkinson's disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population. Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population. Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls...
2015
It has been proposed that European mitochondrial DNA (mtDNA) haplogroups J and K, and their shared 10398G single-nucleotide polymorphism (SNP) in the ND3 gene, are protective from Parkinson’s disease (PD). We evaluated the distribution of the different mtDNA haplogroups in a large cohort of 620 Italian patients with adult-onset (450,o65 years of age) idiopathic PD vs two groups of ethnic-matched controls. Neither the frequencies of haplogroup J nor that of 10398G were significantly different. However, the frequency of haplogroup K was significantly lower in PD. Stratification by sex and age indicated that the difference in the distribution of haplogroup K was more prominent in 450year old males. In spite of the common 10398G SNP, haplogroups J and K belong to widely diverging mitochondrial clades, a consideration that may explain the different results obtained for the two haplogroups in our cohorts. Our study suggests that haplogroup K might confer a lower risk for PD in Italians, c...
Genotyping Parkinson Disease-Associated Mitochondrial Polymorphisms
Clinical Medicine & Research, 2004
The purpose of this study was to establish a system for rapidly detecting single nucleotide polymorphisms (SNPs) in mitochondrial DNA (mtDNA) using hybridization probes and melting temperature (Tm) analysis. This technology should prove useful for population-based studies on the interaction between genetic factors and environmental exposures and the risk of Parkinson disease (PD). METHODS Mitochondrial DNA (mtDNA) was extracted from whole blood. Rapid polymerase chain reaction (PCR) and melting curve analyses were performed with primers and fluorochrome-labeled probes on a LightCycler (Roche Molecular Biochemical, Mannheim, Germany). Genotyping of 10 SNPs in 15 subjects was based on the analysis of allele-specific Tm of detection probes. The results of melting curve analyses were verified by sequencing all 150 PCR products. RESULTS Real-time monitoring showed optimal PCR amplification of each mtDNA fragment. The nucleotide changes at positions 1719,
Mitochondrial Polymorphisms Significantly Reduce the Risk of Parkinson Disease
The American Journal of Human Genetics, 2003
Mitochondrial (mt) impairment, particularly within complex I of the electron transport system, has been implicated in the pathogenesis of Parkinson disease (PD). More than half of mitochondrially encoded polypeptides form part of the reduced nicotinamide adenine dinucleotide dehydrogenase (NADH) complex I enzyme. To test the hypothesis that mtDNA variation contributes to PD expression, we genotyped 10 single-nucleotide polymorphisms (SNPs) that define the European mtDNA haplogroups in 609 white patients with PD and 340 unaffected white control subjects. Overall, individuals classified as haplogroup J (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.34-0.91; ) or K (OR 0.52; 95% CI 0.30-0.90; ) demonstrated a significant decrease in risk of P p .02 P p .02 PD versus individuals carrying the most common haplogroup, H. Furthermore, a specific SNP that defines these two haplogroups, 10398G, is strongly associated with this protective effect (OR 0.53; 95% CI 0.39-0.73; P p ). SNP 10398G causes a nonconservative amino acid change from threonine to alanine within the NADH .0001 dehydrogenase 3 (ND3) of complex I. After stratification by sex, this decrease in risk appeared stronger in women than in men (OR 0.43; 95% CI 0.27-0.71;
Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease
BMC Medical Genetics, 2010
Background: Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. Methods: We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. Results: The frequency of affected mothers of the proband with PD (83/167, 49.4%) was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4%) (Odds Ratio 1.22; 95%CI 0.83-1.81). After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. Conclusions: These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic mDNA mutations, contribute to the risk of familial PD.
Maternal inheritance and mitochondrial DNA variants in familial Parkinson disease
BMC Medical Genetics, 2010
Background: Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. Methods: We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset.
Parkinson's disease and mitochondrial gene variations: A review
Parkinson's disease (PD) is a common disorder of the central nervous system in the elderly. The pathogenesis of PD is a complex process, with genetics as an important contributing factor. This factor may stem from mitochon-drial gene variations and mutations as well as from nuclear gene variations and mutations. More recently, a particular role of mitochondrial dysfunction has been suggested, arising from mitochondrial DNA variations or acquired mutations in PD pathogenesis. The present review summarizes and weighs the evidence in support of mitochondrial DNA (mtDNA) variations as important contributors to the development and course of PD.