Role of mitochondrial DNA variants and copy number in diabetic atherogenesis.
Genet Mol Res
; 11(3): 3339-48, 2012 Sep 17.
Article
en En
| MEDLINE
| ID: mdl-23079827
ABSTRACT
Hyperglycemia-induced reactive oxygen species production can cause diabetes and its complications, including atherosclerosis. The role of mitochondrial DNA variants and mitochondrial copy number in the pathogenesis of diabetic atherogenesis is not well understood. We examined 36 diabetic patients who had undergone amputation for diabetic foot and seven non-diabetic patients who had undergone amputation after traumatic injury. Mitochondrial DNA was extracted and used for sequencing. Single nucleotide polymorphisms (SNPs) relative to the Cambridge reference sequence were analyzed. Mitochondrial DNA copy number was quantified by real-time PCR. Twenty-one novel variants were detected in 29 diabetic patients with arterial stenosis; six of the variants were heteroplasmic, and most occurred in highly evolutionarily conserved residues. These variants were more prevalent in patients with arterial stenosis than in those without stenosis. The novel variants included four in complex I (ND1 C3477A/C, A3523A/G; ND5 C13028A/C, C13060A/C), one in complex IV (COX1 T6090A/T), and one in rRNA (12srRNA G857G/T). Compared with non-diabetic patients, the diabetic patients had significantly less mitochondrial DNA. Furthermore, among diabetic patients with arterial stenosis, there was a significant positive correlation between mitochondrial DNA copy number and the number of total SNPs. In conclusion, we identified six novel heteroplasmic mitochondrial DNA variants among diabetic patients with arterial stenosis, and we found that diabetic atherogenesis is associated with decreased amounts of mitochondrial DNA.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN Mitocondrial
/
Complicaciones de la Diabetes
/
Aterosclerosis
/
Variaciones en el Número de Copia de ADN
Límite:
Humans
Idioma:
En
Revista:
Genet Mol Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Taiwán