TY - JOUR
T1 - Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79958285686&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0021029
DO - 10.1371/journal.pone.0021029
M3 - Article
C2 - 21695278
AN - SCOPUS:79958285686
VL - 6
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e21029
ER -