Mitochondrial DNA Haplogroups Associated with Age-Related Macular Degeneration

Udar, Nitin; Atilano, Shari R.; Memarzadeh, M.; Boyer, David S.; Chwa, Marilyn; Song-nian, LU; Maguen, B.; Langberg, Jonathan; Coşkun, Pınar; Wallace, Douglas C.; Nesburn, Anthony B.; Khatibi, Nikan H.; Hertzog, Dieter; Le, Khoi; Hwang, Daniel S.; Kenney, M. Cristina

doi:10.1167/iovs.08-2646

Cited by 113 publications

(92 citation statements)

References 46 publications

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“…The C16223T variant have been described in infantile sudden death syndrome, schizophrenic patients, age-related macular degeneration, and idiopathic cardiomyopathy [28][29][30][31]. The C16294T variant is associated with Parkinson disease, infantile sudden death syndrome and age-related macular degeneration [29,30]. The T16311C variant is seen in primary prostatic cancer [32].…”

Section: Discussionmentioning

confidence: 99%

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No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

Seyedhassani

Houshmand

Kalantar

et al. 2010

J Assist Reprod Genet

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Purpose Repeated pregnancy loss (RPL) occurs in 1 out of 300 couples, and the cause of about 50% of them remains idiopathic. Mitochondria have an important role in human development through ATP production and their involvement in apoptosis. Methods 96 RPL and 96 control females were used to investigate the frequency of deletions and point mutations in the displacement loop (D-loop) on mitochondria. Multiplex PCR and DNA sequencing methods were used to detect possible variations in the mitochondrial DNA (mtDNA).Results No deletions but a high frequency of point mutations were found in RPL females; among 129 variations observed in RPL, 22 mutations were significant (P<0.05) and the insertion of C in nucleotide 114 was novel. Conclusion High rate of mutations in D-loop of mtDNA was observed in maternal blood, a fact that may have a direct or indirect role in inducing RPL. The results can be used in the assessment of RPL and designing possible treatments for improving assisted reproduction.

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Section: Discussionmentioning

confidence: 99%

“…Such polymorphism is also described in H, U and K haplogroups. The role of haplogroups is emphasized for various disorders such as age-related macular degeneration [30]. This mutation can increase the risk of Parkinson disease as a variation associated with haplogroup H [37].…”

Section: Discussionmentioning

confidence: 99%

No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

Seyedhassani

Houshmand

Kalantar

et al. 2010

J Assist Reprod Genet

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Section: Adaptive Mtdna Variantsmentioning

confidence: 99%

“…Haplogroup H correlates with reduced risk of age-related macular degeneration, while haplogroups J and U are associated with increased risk of macular degeneration as well as increased drusen levels and retinal pigment abnormalities (Jones et al 2007;Udar et al 2009). Haplogroup H and H-nt 4336 are associated with increased risk, and haplogroups J and Uk with decreased risk, for developing PD (Shoffner et al 1993;van der Walt et al 2003;Ghezzi et al 2005;Khusnutdinova et al 2008). The haplogroup H-nt 4336 sublineage is also associated with increased AD risk, while haplogroups U and T are associated with decreased risk in certain contexts (Shoffner et al 1993;Chagnon et al 1999;Carrieri et al 2001;van der Walt et al 2004).…”

Section: Adaptive Mtdna Variantsmentioning

confidence: 99%

The pathophysiology of mitochondrial disease as modeled in the mouse

Wallace¹,

Fan²

2009

Genes Dev.

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184

150

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It is now clear that mitochondrial defects are associated with a plethora of clinical phenotypes in man and mouse. This is the result of the mitochondria's central role in energy production, reactive oxygen species (ROS) biology, and apoptosis, and because the mitochondrial genome consists of roughly 1500 genes distributed across the maternal mitochondrial DNA (mtDNA) and the Mendelian nuclear DNA (nDNA). While numerous pathogenic mutations in both mtDNA and nDNA mitochondrial genes have been identified in the past 21 years, the causal role of mitochondrial dysfunction in the common metabolic and degenerative diseases, cancer, and aging is still debated. However, the development of mice harboring mitochondrial gene mutations is permitting demonstration of the direct cause-and-effect relationship between mitochondrial dysfunction and disease. Mutations in nDNA-encoded mitochondrial genes involved in energy metabolism, antioxidant defenses, apoptosis via the mitochondrial permeability transition pore (mtPTP), mitochondrial fusion, and mtDNA biogenesis have already demonstrated the phenotypic importance of mitochondrial defects. These studies are being expanded by the recent development of procedures for introducing mtDNA mutations into the mouse. These studies are providing direct proof that mtDNA mutations are sufficient by themselves to generate major clinical phenotypes. As more different mtDNA types and mtDNA gene mutations are introduced into various mouse nDNA backgrounds, the potential functional role of mtDNA variation in permitting humans and mammals to adapt to different environments and in determining their predisposition to a wide array of diseases should be definitively demonstrated.

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“…All non-African lineages belong to two founder clusters, namely haplogroups M and N; 489C, defined as haplogroup M, and 489T, defined as haplogroup N. According to the 'out of Africa' theory, these are both derived from the L3 mtDNA African lineage (30). The functional significance of the mtDNA haplogroups and their association with human behaviors requires further study, although certain haplogroups have been identified as markers for special diseases (31,32). The results from this study require validation in the form of larger population sizes and laboratory-based functional studies.…”

Section: Of Cases (Years) -------------------------------------------mentioning

confidence: 99%

Mitochondrial DNA haplogroup M is associated with late onset of hepatocellular carcinoma

Guo

Yang

Wang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been associated with various types of cancer. The association of SNPs with cancer risk and disease outcome has been exhaustively studied. In this study, we investigated the association of age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of hepatocellular carcinoma (HCC) patients. Haplogroup M (489C) and allele 235G were identified for their association with the late onset of HCC by the log-rank test. In an overall multivariate analysis, haplogroup M (489C) was identified as an independent predictive factor for the age-at-onset of HCC at borderline significant levels [relative risk, 1.736; 95% confidence interval (CI), 0.967-3.115; p= 0.065]. Genetic polymorphisms in the D-loop are predictive markers for age-at-onset in HCC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help to identify HCC patient subgroups at high risk of early onset of the disease.

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Mitochondrial DNA Haplogroups Associated with Age-Related Macular Degeneration

Abstract: AMD retinas exhibited increased mtDNA control region SNPs compared to normal retinas. This correlated with an increased frequency of mtDNA SNPs associated with haplogroups J, T and U in patients with AMD. These results implicate mitochondrial alterations in the etiology of AMD.

Cited by 113 publications

References 46 publications

No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

The pathophysiology of mitochondrial disease as modeled in the mouse

Mitochondrial DNA haplogroup M is associated with late onset of hepatocellular carcinoma

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