Detailed Analysis of Variation at and around Mitochondrial Position 16189 in a Large Finnish Cohort Reveals No Significant Associations with Early Growth or Metabolic Phenotypes at Age 31 Years

Das, Sreena; Bennett, Amanda J.; Sovio, Ulla; Ruokonen, Aimo; Martikainen, Hannu; Pouta, Anneli; Hartikainen, Anna-Liisa; Elliott, Paul; Poulton, Joanna; Järvelin, Marjo‐Riitta; McCarthy, Mark I.

doi:10.1210/jc.2007-0702

Cited by 17 publications

(16 citation statements)

References 27 publications

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“…According to our knowledge, LDL and HDL levels have been taken into consideration in a limited numbers of studies and no significant association was found. 14,15 Our study has several limitations. Firstly, mean age of patients and healthy controls and the number of cases participating in the study cohort are relatively lower than previous studies.…”

Section: Discussionmentioning

confidence: 94%

“…8,25 However, others failed to find associations between metabolic phenotypes and this variant. 15,22,26 Despite these findings, it is still questionable if this variant has a direct effect on the pathogenesis of type II DM or metabolic syndrome. An explanation for this inconsistency might be that the prevalence of the T16189C polymorphism is higher in Asia than in Europe and that the power of a polymorphism to influence disease outcome is dependent on its frequency in the population.…”

Section: Discussionmentioning

confidence: 99%

“…14 In contrast, Das et al 15 showed that there was no association of the mtDNA 16189 variant with metabolic diseases in a large cohort of a Finnish population. Likewise, Saxena et al 16 showed no association between common mtDNA variants and type II DM and BMI in European samples.…”

Section: Introductionmentioning

confidence: 96%

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Investigation of relationship of the mitochondrial DNA 16189 T>C polymorphism with metabolic syndrome and its associated clinical parameters in Turkish patients

Aral¹,

Akkiprik²,

Çağlayan³

et al. 2011

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ObJEctIVE: Mitochondrial DNA (mtDNA) polymorphisms have been implicated in the pathophysiology of human diseases. Among them, a t>c nucleotide transition on the 16189 nucleotide position of mtDNA has been studied in several metabolic diseases including diabetes and obesity. In this study we aimed to investigate the association of this polymorphism among turkish metabolic syndrome patients. DEsIGN: A total of 220 cases (70 Mets patients and 150 healthy control subjects) were evaluated for their mtDNA 16189 variant by Pcr-rFLP technique. In addition, clinical and biochemical variables, such as cholesterol levels, body fat percentage, insulin resistance and presence of type II diabetes, were also evaluated. rEsULts: Overall frequency of polymorphic c allele was determined as 0.19 without a significant association with type II diabetes and metabolic syndrome. this may be partly due to ethnical differences of populations studied and may also be related to other genetic and environmental factors. Moreover, there were no significant associations with biochemical variables among metabolic syndrome patients, except LDL and suppressed cortisol (sup-cortisol) levels. Low levels of LDL and sup-cortisol were significantly associated with the mtDNA 16189 variant, though the biochemical mechanism underlying this effect is not clear. cONcLUsIONs: this is the first study involving a turkish population on the mtDNA 16189 t>c polymorphism. Further studies with larger cohorts will be needed to elucidate its relation with metabolic syndrome as well as lipid metabolism.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Investigation of relationship of the mitochondrial DNA 16189 T>C polymorphism with metabolic syndrome and its associated clinical parameters in Turkish patients

Aral¹,

Akkiprik²,

Çağlayan³

et al. 2011

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“…Although some recent case-control studies in Europe could not replicate the association between the 16189 variant and T2D [86][87][88][89], a multinational study in Asians including 2,469 T2D patients and 1,205 controls from Korea, Japan, Taiwan, Hong Kong, and China confirmed the role of the mtDNA 16189 variant at least in Asian T2D patients [90]. The prevalence rate of the 16189 variant of mtDNA in Taiwan Chinese adults was 38.2% (34.6% in non-diabetic and 43.1% in diabetic subjects) [84].…”

Section: Mitochondrial Dna Variants and Diabetes Mellitusmentioning

confidence: 98%

Mitochondrial DNA Variants in the Pathogenesis of Type 2 Diabetes - Relevance of Asian Population Studies

Wang

Lin²,

Weng³

et al. 2009

Rev Diabet Stud

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■ AbstractMitochondrial dysfunction involves defective insulin secretion by pancreatic beta-cells, and insulin resistance in insulin-sensitive tissues such as muscle and adipose tissue. Mitochondria are recognized as the most important cellular source of energy, and the major generator of intracellular reactive oxygen species (ROS). Intracellular antioxidative systems have been developed to cope with increased oxidative damage. In case of minor oxidative stress, the cells may increase the number of mitochondria to produce more energy. A mechanism called mitochondrial biogenesis, involving several transcription factors and regulators, controls the quantity of mitochondria. When oxidative damage is advanced beyond the repair capacity of antioxidative systems, then oxidative stress can lead to cell death. Therefore, this organelle is central to cell life or death. Available evidence increasingly shows genetic linkage between mitochondrial DNA (mtDNA) alterations and type 2 diabetes (T2D). Based on previous studies, the mtDNA 16189 variant is associated with metabolic syndrome, higher fasting insulin concentration, insulin resistance index and lacunar cerebral infarction. These data support the involvement of mitochondrial genetic variation in the pathogenesis of T2D. Importantly, phylogeographic studies of the human mtDNAs have revealed that the human mtDNA tree is rooted in Africa and radiates into different geographic regions and can be grouped as haplogroups. The Asian populations carry very different mtDNA haplogroups as compared to European populations. Therefore, it is critically important to determine the role of mtDNA polymorphisms in T2D.

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“…Indeed, a variant at position 16189 has been shown to be associated with elevated fasting insulin concentrations (Poulton et al, 2002;Poulton et al, 1998) and Type 2 Diabetes in a population-based casecontrol study (Poulton et al, 2002). However, other studies have been unable to replicate this association (Chinnery et al, 2005;Das et al, 2007;Mohlke et al, 2005). Moreover, another study aimed to capture the entire common variation (except the hypervariable D-loop) in mtDNA with a frequency >1%, and test if any of these variants are associated with Type 2 Diabetes (Saxena et al, 2006); 3304 cases and 3304 matched control subjects were examined.…”

Section: Genetic and Epigenetic Regulation Of Mitochondria And Associmentioning

confidence: 99%

Mitochondrial dysfunction in pancreatic β-cells in Type 2 Diabetes

Mulder

Ling

2009

Molecular and Cellular Endocrinology

105

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Mitochondrial metabolism controls insulin secretion from the pancreatic β-cell. Type 2 Diabetes evolves when the β-cells fail to release appropriate amounts of insulin, causing metabolic dysregulation and hyperglycemia. It is attractive to assume that mitochondrial dysfunction plays a decisive role in these processes. Indeed, while being a rare condition, genetically determined dysfunction of mitochondria causes a Type 2 Diabetes-like syndrome.Here, we review what is known about mitochondrial dysfunction in the β-cell in Type 2Diabetes. The focus is on observations in humans but relevant studies in animal models of the disease are discussed. A particular emphasis is placed on changes in metabolic enzymes and function in β-cell mitochondria and how altered structure of the organelle appears to facilitate its function. These molecular processes are subject to tight genetic as well as epigenetic control. Variations and implications of these mechanisms are reviewed. The emerging picture is that alterations in mitochondria may be a culprit in the pathogenetic processes culminating in Type 2 Diabetes. Such processes may prove to be targets for therapeutic interventions in the disease.

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Detailed Analysis of Variation at and around Mitochondrial Position 16189 in a Large Finnish Cohort Reveals No Significant Associations with Early Growth or Metabolic Phenotypes at Age 31 Years

Abstract: Despite substantial power to detect previously reported effects, mtDNA variations around OriB are not major contributors to variation in early growth and metabolic phenotypes during early adulthood.

Cited by 17 publications

References 27 publications

Investigation of relationship of the mitochondrial DNA 16189 T>C polymorphism with metabolic syndrome and its associated clinical parameters in Turkish patients

Investigation of relationship of the mitochondrial DNA 16189 T>C polymorphism with metabolic syndrome and its associated clinical parameters in Turkish patients

Mitochondrial DNA Variants in the Pathogenesis of Type 2 Diabetes - Relevance of Asian Population Studies

Mitochondrial dysfunction in pancreatic β-cells in Type 2 Diabetes

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