Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole

Alessandro Achilli, Anna Olivieri, Maria Pala, Baharak Hooshiar Kashani, Valeria Carossa, Ugo A. Perego, Francesca Gandini, Aurelia Santoro, Vincenza Battaglia, Viola Grugni, Hovirag Lancioni, Cristina Sirolla, Anna Rita Bonfigli, Antonella Cormio, Massimo Boemi, Ivano Testa, Ornella Semino, Antonio Ceriello, Liana Spazzafumo, Maria Nicola Gadaleta & 4 others Maurizio Marra, Roberto Testa, Claudio Franceschi, Antonio Torroni

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure.

Original languageEnglish
Article numbere21029
JournalPLoS One
Volume6
Issue number6
DOIs
Publication statusPublished - 15 Jun 2011
Externally publishedYes

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Diabetes Complications
Medical problems
Mitochondrial DNA
diabetes
mitochondrial DNA
Genes
retinal diseases
Mitochondrial Genome
peripheral nervous system diseases
renal failure
Phylogeny
Ports and harbors
kidney diseases
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Italy
Population
Renal Insufficiency
protective effect
pathogenesis

Cite this

Achilli, A., Olivieri, A., Pala, M., Kashani, B. H., Carossa, V., Perego, U. A., ... Torroni, A. (2011). Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole. PLoS One, 6(6), [e21029]. https://doi.org/10.1371/journal.pone.0021029
Achilli, Alessandro ; Olivieri, Anna ; Pala, Maria ; Kashani, Baharak Hooshiar ; Carossa, Valeria ; Perego, Ugo A. ; Gandini, Francesca ; Santoro, Aurelia ; Battaglia, Vincenza ; Grugni, Viola ; Lancioni, Hovirag ; Sirolla, Cristina ; Bonfigli, Anna Rita ; Cormio, Antonella ; Boemi, Massimo ; Testa, Ivano ; Semino, Ornella ; Ceriello, Antonio ; Spazzafumo, Liana ; Gadaleta, Maria Nicola ; Marra, Maurizio ; Testa, Roberto ; Franceschi, Claudio ; Torroni, Antonio. / Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole. In: PLoS One. 2011 ; Vol. 6, No. 6.
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Achilli, A, Olivieri, A, Pala, M, Kashani, BH, Carossa, V, Perego, UA, Gandini, F, Santoro, A, Battaglia, V, Grugni, V, Lancioni, H, Sirolla, C, Bonfigli, AR, Cormio, A, Boemi, M, Testa, I, Semino, O, Ceriello, A, Spazzafumo, L, Gadaleta, MN, Marra, M, Testa, R, Franceschi, C & Torroni, A 2011, 'Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole', PLoS One, vol. 6, no. 6, e21029. https://doi.org/10.1371/journal.pone.0021029

Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole. / Achilli, Alessandro; Olivieri, Anna; Pala, Maria; Kashani, Baharak Hooshiar; Carossa, Valeria; Perego, Ugo A.; Gandini, Francesca; Santoro, Aurelia; Battaglia, Vincenza; Grugni, Viola; Lancioni, Hovirag; Sirolla, Cristina; Bonfigli, Anna Rita; Cormio, Antonella; Boemi, Massimo; Testa, Ivano; Semino, Ornella; Ceriello, Antonio; Spazzafumo, Liana; Gadaleta, Maria Nicola; Marra, Maurizio; Testa, Roberto; Franceschi, Claudio; Torroni, Antonio.

In: PLoS One, Vol. 6, No. 6, e21029, 15.06.2011.

Research output: Contribution to journalArticle

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AU - Achilli, Alessandro

AU - Olivieri, Anna

AU - Pala, Maria

AU - Kashani, Baharak Hooshiar

AU - Carossa, Valeria

AU - Perego, Ugo A.

AU - Gandini, Francesca

AU - Santoro, Aurelia

AU - Battaglia, Vincenza

AU - Grugni, Viola

AU - Lancioni, Hovirag

AU - Sirolla, Cristina

AU - Bonfigli, Anna Rita

AU - Cormio, Antonella

AU - Boemi, Massimo

AU - Testa, Ivano

AU - Semino, Ornella

AU - Ceriello, Antonio

AU - Spazzafumo, Liana

AU - Gadaleta, Maria Nicola

AU - Marra, Maurizio

AU - Testa, Roberto

AU - Franceschi, Claudio

AU - Torroni, Antonio

PY - 2011/6/15

Y1 - 2011/6/15

N2 - Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure.

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