The European‐Specific Mitochondrial Cluster J/T Could Confer an Increased Risk of Insulin‐Resistance and Type 2 Diabetes: An Analysis of the m.4216T &gt; C and m.4917A &gt; G Variants

Crispim, Daisy; Canani, Luís Henrique Santos; Gross, Jorge Luiz; Tschiedel, Balduíno; Souto, Kátia Elisabete Pires; Roisenberg, Israel

doi:10.1111/j.1469-1809.2005.00249.x

Cited by 64 publications

(35 citation statements)

References 30 publications

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“…This compact genome is maternally inherited, has a high mutation rate, and does not undergo recombination. Mitochondria are essential to cellular metabolism, and mtDNA variation has been associated with multiple complex diseases including cancer (Canter et al 2005; Wallace 2012; Zheng et al 2012), type 2 diabetes (Wang et al 2001; Crispim et al 2006; Tang et al 2006; Soini et al 2012), and neurological disorders such as Parkinson’s and Alzheimer’s (van der Walt et al 2003; van der Walt et al 2004). Additionally, epidemiologic studies indicate that some common complex diseases, such as diabetes (Alcolado and Alcolado 1991; Thomas et al 1994; Young et al 1995) and preterm birth (Alleman et al 2012), exhibit strong maternal inheritance supporting the notion that mitochondrial genome variation could contribute to underlying disease etiology.…”

Section: Introductionmentioning

confidence: 99%

Characterization of mitochondrial haplogroups in a large population-based sample from the United States

et al. 2014

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Mitochondrial DNA (mtDNA) haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian mitochondrial haplogroup lineages. Using these mtDNA markers we constructed a mitochondrial haplogroup classification tree and classified 18,832 participants from the National Health and Nutrition Examination Surveys (NHANES). To our knowledge, this is the largest study to date characterizing mitochondrial haplogroups in a population-based sample from the United States, and the first study characterizing mitochondrial haplogroup distributions in self-identified Mexican Americans separately from Hispanic Americans of other descent. We observed clear differences in the distribution of maternal genetic ancestry consistent with proposed admixture models for these subpopulations, underscoring the genetic heterogeneity of the United States Hispanic population. The mitochondrial haplogroup distributions in the other self-identified racial/ethnic groups within NHANES were largely comparable to previous studies. Mitochondrial haplogroup classification was highly concordant with self-identified race/ethnicity (SIRE) in non-Hispanic whites (94.8%), but was considerably lower in admixed populations including non-Hispanic blacks (88.3%), Mexican Americans (81.8%), and other Hispanics (61.6%), suggesting SIRE does not accurately reflect maternal genetic ancestry, particularly in populations with greater proportions of admixture. Thus, it is important to consider inconsistencies between SIRE and genetic ancestry when performing genetic association studies. The mitochondrial haplogroup data that we have generated, coupled with the epidemiologic variables in NHANES, is a valuable resource for future studies investigating the contribution of mtDNA variation to human health and disease.

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Section: Introductionmentioning

confidence: 99%

Characterization of mitochondrial haplogroups in a large population-based sample from the United States

et al. 2014

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“…4 Haplogroup J is of particular interest because of a recently reported association with insulin resistance and type 2 diabetes in a Brazilian study of 347 patients and 350 controls. 5 Given the potential importance of these controversial findings, we carried out an independent study of 897 cases of type 2 diabetes and 1010 controls based on a conventional haplogroup-association design, aimed at identifying deep-rooted ancient genetic variants of mtDNA that predispose to type 2 diabetes, or clades containing one or more recent functional variants that contribute to the risk of the disorder.…”

mentioning

confidence: 99%

Mitochondrial DNA haplogroups and type 2 diabetes: a study of 897 cases and 1010 controls

Chinnery

Mowbray

Patel

et al. 2007

Journal of Medical Genetics

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Mitochondria play a central role in the secretion of insulin by pancreatic beta-cells, and pathogenic mutations of mitochondrial DNA (mtDNA) can cause diabetes. The aetiology of type 2 diabetes has a strong genetic component, raising the possibility that genetic variants of mtDNA alter the risk of developing the disorder. Recent studies have produced conflicting results. By studying 897 UK cases of type 2 diabetes and 1010 population-matched controls, it is shown that European mtDNA haplogroups are unlikely to play a major role in the risk of developing the disorder.

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“…Recent data indicate that polymorphisms of the mitochondrial genome (mtDNA) are not neutral and evidence of an association between mtDNA variability and complex traits is increasing (Wallace 2005;Crispim et al 2006;Bai et al 2007). Furthermore, numerous evidences suggest that the different mtDNA lineages are qualitatively different from each other, bearing mutations that can modulate mitochondrial function and consequently influence complex phenotypes (Mishmar et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Bellizzi

Taverna

D’Aquila

et al. 2009

Cell Stress and Chaperones

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To explore possible relationships between mitochondrial DNA (mtDNA) polymorphism and the expression levels of stress-responder nuclear genes we assembled five cybrid cell lines by repopulating 143B.TK − cells, depleted of their own mtDNA (Rho 0 cells), with foreign mitochondria with different mtDNA sequences (lines H, J, T, U, X). We evaluated, at both basal and under heat stress conditions, gene expression (mRNA) and intra-mitochondrial protein levels of HSP60 and HSP75, two key components in cellular stress response. At basal conditions, the levels of HSP60 and HSP75 mRNA were lower in one cybrid (H) than in the others (p=0.005 and p=0.001, respectively). Under stress conditions, the H line over-expressed both genes, so that the inter-cybrid difference was abolished. Moreover, the HSP60 intra-mitochondrial protein levels differed among the cybrid lines (p=0.001), with levels higher in H than in the other cybrid lines. On the whole, our results provide further experimental evidence that mtDNA variability influences the cell response to stressful conditions by modulating components involved in this response. Sentence summary of the article: the results reported in the present study provide important experimental evidence that in human cells mtDNA variability is able to influence the cellular response to heat stress by modulating both the transcription of genes involved in this response and their intra-mitochondrial protein levels.

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The European‐Specific Mitochondrial Cluster J/T Could Confer an Increased Risk of Insulin‐Resistance and Type 2 Diabetes: An Analysis of the m.4216T > C and m.4917A > G Variants

Cited by 64 publications

References 30 publications

Characterization of mitochondrial haplogroups in a large population-based sample from the United States

Characterization of mitochondrial haplogroups in a large population-based sample from the United States

Mitochondrial DNA haplogroups and type 2 diabetes: a study of 897 cases and 1010 controls

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

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