title: Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole.
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.
authors.affiliation: Dipartimento di Biologia Cellulare e Ambientale, Università di Perugia, Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Achilli
authors.forename: Anna
authors.initials: A
authors.lastname: Olivieri
authors.forename: Maria
authors.initials: M
authors.lastname: Pala
authors.forename: Baharak
authors.initials: B
authors.lastname: Hooshiar Kashani
authors.forename: Valeria
authors.initials: V
authors.lastname: Carossa
authors.forename: Ugo A
authors.initials: UA
authors.lastname: Perego
authors.forename: Francesca
authors.initials: F
authors.lastname: Gandini
authors.forename: Aurelia
authors.initials: A
authors.lastname: Santoro
authors.forename: Vincenza
authors.initials: V
authors.lastname: Battaglia
authors.forename: Viola
authors.initials: V
authors.lastname: Grugni
authors.forename: Hovirag
authors.initials: H
authors.lastname: Lancioni
authors.forename: Cristina
authors.initials: C
authors.lastname: Sirolla
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bonfigli
authors.forename: Antonella
authors.initials: A
authors.lastname: Cormio
authors.forename: Massimo
authors.initials: M
authors.lastname: Boemi
authors.forename: Ivano
authors.initials: I
authors.lastname: Testa
authors.forename: Ornella
authors.initials: O
authors.lastname: Semino
authors.forename: Antonio
authors.initials: A
authors.lastname: Ceriello
authors.forename: Liana
authors.initials: L
authors.lastname: Spazzafumo
authors.forename: Maria Nicola
authors.initials: MN
authors.lastname: Gadaleta
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marra
authors.forename: Roberto
authors.initials: R
authors.lastname: Testa
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Antonio
authors.initials: A
authors.lastname: Torroni
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D048909:Diabetes Complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D054629:Genome, Mitochondrial / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny
chemical_list: D004272:DNA, Mitochondrial