Table 1.
Clinical characteristics of diabetic patients and controls.
Table 2.
Frequencies of the major mitochondrial DNA haplogroups and sub-haplogroups in diabetic patients and controls.
Figure 1.
Schematic phylogeny of haplogroup R0a encompassing seven complete mtDNA sequences from diabetic patients.
The schematic classification of the R0a sub-clades is based on Černý et al. [42], while the R0a'b node is newly defined on the basis of the complete genome #7. Sequences #1–7 were obtained in the course of this study and are from Italian diabetic patients: sequences #1–6 (GenBank accession numbers JF717355-JF717360) are from subjects of the Marche region sample, while sequence #7 (GenBank accession number JF717361) is from a diabetic patient not included in the current study because the maternal ancestry was from a different region (Campania, Southern Italy). Three control mtDNA sequences from the literature (GenBank accession numbers HM185239, HM185241 [42] and AY738940 [20]), which clustered in the same sub-branches of the sequences obtained from the diabetic subjects, were also included in the tree. The position of the revised Cambridge Reference Sequence (rCRS) [43] – a member of haplogroup H2a2 – is indicated for reading off sequence motifs. Mutations are shown on the branches; they are transitions unless a base is explicitly indicated. The prefix @ designates reversions, while suffixes indicate transversions (to A, G, C, or T), insertions (+), gene locus (∼t, tRNA; ∼r, rRNA; nc, non coding region outside of the control region) and synonymous or non synonymous changes (s or ns). Recurrent mutations within the phylogeny are underlined.
Table 3.
Frequencies of mtDNA haplogroups and sub-haplogroups in patients with only the diabetic phenotype and diabetic patients also affected by at least one or two of six common complications [retinopathy, somatic neuropathy, cardiac ischemia, nephropathy, peripheral artery occlusive disease (PAOD), and/or renal failure].
Table 4.
Logistic-regression analyses of haplogroups associated with T2DM complications.
Table 5.
“Inverted” logistic-regression analyses employed to evaluate characteristics associated with candidate haplogroups.
Figure 2.
MtDNA tree encompassing the roots of haplogroups associated with T2DM and/or its complications.
The distinguishing mutational motifs for the haplogroups shown in the tree are reported on the branches and they are transitions unless a base is explicitly indicated. The position of the rCRS [43] is indicated for reading off sequence motifs. Suffixes indicate transversions (to A), insertions (+), synonymous or non-synonymous changes (s or ns), gene locus (for tRNA, rRNA and non-synonymous mutations – following the nomenclature proposed by MITOMAP). A role for haplogroups R0a/R0a2, H, H1, H3/H3 h, V, and U3/U3a has been proposed in this study. The protective or pejorative haplogroup effect is indicated by down or up arrows. Continuous arrow lines mean highly significant values. Previous analyses found associations (gray arrows) with J1 [13], JT and T [14], and N9a [11], [12].
Table 6.
Power values calculated for each haplogroup in different comparisons.