Increased risk of stroke in patients with the A12308G polymorphism in mitochondria

Pulkes, Teeratorn; Sweeney, MG; Hanna, Michael G.

doi:10.1016/s0140-6736(00)03408-5

Cited by 50 publications

(29 citation statements)

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“…The significance of homoplasmic variations in mtDNA remains uncertain though several homoplasmic mutations have been implied in disease processes. Indeed, certain mtDNA variants have been demonstrated to either ameliorate (El Meziane et al, 1998) or worsen (Pulkes et al, 2001) the clinical picture of patients already affected with known mitochondrial mutations, or to increase the susceptibility to severe cardiac diseases in apparently healthy populations (Shin et al, 2000;Khogali et al, 2001). In addition, the presence of a non-synonymous homoplasmic mtDNA mutation has been recently associated with severe COX deficiency, multiple neonatal deaths and Leigh syndrome (McFarland et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

A collection of 33 novel human mtDNA homoplasmic variants

et al. 2002

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Mitochondria are involved in cellular energy production via oxidative phosphorylation and this function may be damaged by any mutation in mitochondrial DNA (mtDNA). To identify novel mtDNA mutations, we have developed a program to systematically screen the entire mitochondrial genome in a large number of individuals with clinical and/or morphological features of mitochondrial dysfunction, but still no genetic diagnosis. The sequence-data were obtained with an automated rapid system, which gave us a series of information: in the eleven mitochondrial genomes analyzed we observed the presence of 33 differences from the revised Cambridge Reference Sequence (Andrews et al., 1999), but they were all homoplasmic in the patients' tissues analyzed (skeletal muscle and blood), suggesting that they are unlikely to be primarily pathogenic though they may be co-responsible in the determination of the disease. This work can therefore help complete the already ample mtDNA polymorphism existent database.

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Section: Resultsmentioning

confidence: 99%

A collection of 33 novel human mtDNA homoplasmic variants

et al. 2002

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“…24 There have been a few studies addressing the associations between mitochdrial polymorphism and diseases, [25][26][27][28][29] but further studies are needed to clarify the role of the mitochodrial genotype in common diseases. The Framingham longevity study of coronary heart disease has indicated that longevity is more strongly associated with age of maternal death than that of paternal death.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial 5178A/C Genotype is Associated With Acute Myocardial Infarction.

Mukae

Aoki

Itoh

et al. 2003

Circ J

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ardiovascular diseases are thought to result from the interaction of multiple environmental and genetic factors. [1][2][3] The ECTIM study showed that the ACE DD genotype was more frequent in patients with myocardial infarction than in control subjects, 4 and Tiret et al also showed that the association between the ACE DD genotype and myocardial infarction was increased in a subset of patients who also carried the angiotensin II type 1 C allele. 5 Other studies have confirmed the association of the ACE D allele and angiotensin II type 1 receptor C allele with an increased risk of myocardial infarction, 6-10 and furthermore, there have been several reports of the association of some nuclear genes with coronary heart diseases in Japanese subjects. 11-13 However, few have addressed the association between polymorphisms of the mitochondria (mt) and coronary heart disease.Human mitochondrial DNA (mtDNA) consists of 16,569 base pairs (bp) located on the circular double strand of the H-and L-chains: 13 types of proteins, 22 types of transfer RNA (tRNA) and 2 types of liposome RNAs are densely coded in a region other than the non-coding region of approximately 1 kb. The mtDNA is highly polymorphic and controls the oxidative phosphorylation system regulating the oxygen metabolism.Tanaka et al reported a mutation specifically seen in Japanese subjects at nucleotide 5178 within the NADH dehydrogenase in the mitochondrial electron transport system Complex 1; mitochdrial 5178A/C is involved in a Met to Leu substitution. [14][15][16][17][18] According to them, the ratio of adenine (A) is approximately half that in healthy people and Japanese centenarians mostly carry A at 5178, which is rarely seen in Europeans or non-Japanese Asians. Based on their findings, they suggested that the high ratio of 5178A may be specific to the Japanese population and possibly related to the fact that the life expectancy at birth in Japan is among the highest in the world.Maternally transmitted mitochondrial genotypes may influence oxidative damage and 5178A/C may be relevant to common diseases. The aim of the present research was to examine the association between genetic factors and the incidence of myocardial infarction. In particular, we focused on the association between mitochondrial genotypes and coronary heart disease; in order to demonstrate a contribution of mitochondrial single nucleotide polymorphisms (SNPs) to the susceptibility to acute myocardial infarction (AMI), we investigated the association of mitochondrial 5178A/C polymorphism with the occurrence of AMI. Methods Study PopulationParticipants were randomly selected inpatients and outpatients treated at the University Hospital and affiliated hospitals in Tokyo, Japan. We divided the study subjects, all of them Japanese, into 4 groups.(1) AMI group, which consisted of 150 patients (102 men, mean age: 64 years old) who underwent coronary angiography at our University Hospital from 1997 to 1999. AMI was diagnosed from clinical evidence of cardiac attack, electrocardiographic findi...

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“…Pathogenic expression of homoplasmic mtDNA mutations may also need a complex nuclear-mitochondrial interaction (8). Studies have suggested that mtDNA polymorphisms are associated with a variety of disorders, including Alzheimer's disease (9), acute myocardial infarction (10), bipolar disorder (11), Leber's hereditary optic neuropathy (6,12), sensorineural hearing impairment (13,14), Parkinson's disease (15)(16)(17)(18), stroke (19,20), and Wolfram (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome (21,22). Most of these studies focused on one or limited number of mtDNA single-nucleotide polymorphisms (SNP).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Genetic Background Modifies Breast Cancer Risk

et al. 2007

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Inefficient mitochondrial electron transport chain (ETC) function has been implicated in the vicious cycle of reactive oxygen species (ROS) production that may predispose an individual to late onset diseases, such as diabetes, hypertension, and cancer. Mitochondrial DNA (mtDNA) variations may affect the efficiency of ETC and ROS production, thus contributing to cancer risk. To test this hypothesis, we genotyped 69 mtDNA variations in 156 unrelated EuropeanAmerican females with familial breast cancer and 260 agematched European-American female controls. Fisher's exact test was done for each single-nucleotide polymorphism (SNP)/ haplogroup and the P values were adjusted for multiple testing using permutation. Odds ratio (OR) and its 95% confidence interval (95% CI) were calculated using the Sheehe correction. Among the 69 variations, 29 were detected in the study subjects. Three SNPs, G9055A (OR, 3.03; 95% CI, 1.63-5.63; P = 0.0004, adjusted P = 0.0057), A10398G (OR, 1.79; 95% CI, 1.14-2.81; P = 0.01, adjusted P = 0.19), and T16519C (OR, 1.98; 95% CI, 1.25-3.12; P = 0.0030, adjusted P = 0.0366), were found to increase breast cancer risk; whereas T3197C (OR, 0.31; 95% CI, 0.13-0.75; P = 0.0043, adjusted P = 0.0526) and G13708A (OR, 0.47; 95% CI, 0.24-0.92; P = 0.022, adjusted P = 0.267) were found to decrease breast cancer risk. Overall, individuals classified as haplogroup K show a significant increase in the risk of developing breast cancer (OR, 3.03; 95% CI, 1.63-5.63; P = 0.0004, adjusted P = 0.0057), whereas individuals bearing haplogroup U have a significant decrease in breast cancer risk (OR, 0.37; 95% CI, 0.19-0.73; P = 0.0023, adjusted P = 0.03). Our results suggest that mitochondrial genetic background plays a role in modifying an individual's risk to breast cancer. [Cancer Res 2007;67(10):4687-94]

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Increased risk of stroke in patients with the A12308G polymorphism in mitochondria

Cited by 50 publications

References 5 publications

A collection of 33 novel human mtDNA homoplasmic variants

A collection of 33 novel human mtDNA homoplasmic variants

Mitochondrial 5178A/C Genotype is Associated With Acute Myocardial Infarction.

Mitochondrial Genetic Background Modifies Breast Cancer Risk

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