Mitochondrial DNA copy number is modulated by geneticvariation in the signal transducer and activator of transcription 3 (STAT3)

TOMAS FERNÁNDEZ GIANOTTI; GUSTAVO CASTAÑO; CAROLINA GEMMA; ADRIANA L. BURGUEÑO; MARIA SOLEDAD ROSSELLI; CARLOS J PIROLA; SILVIA SOOKOIAN

METABOLISM-CLINICAL AND EXPERIMENTAL

W B SAUNDERS CO-ELSEVIER INC

Lugar: Amsterdam; Año: 2011 vol. 60 p. 1142 - 1149

0026-0495

The regulation of mitochondrial DNA (mtDNA) copy number not only is critical for themaintenance of the normal mitochondrial function but has a strong clinical significance. Arecent report revealed that the signal transducer and activator of transcription 3 (STAT3) isinvolved in the regulation of the mitochondrial function and is required for the optimalfunction of the electron transport chain. In this study, we explored whether gene variants inthe STAT3 influence the leukocyte mtDNA copy number. Clinical data and blood sampleswere collected from 179 subjects (aged 52.8 ± 0.9 years). Mitochondrial DNA quantificationusing nuclear DNA (nDNA) as a reference was carried out by a real-time quantitativepolymerase chain reaction method; results are presented as the mtDNA/nDNA ratio. Weselected 3 tag single nucleotide polymorphisms showing a minor allele frequency greaterthan 10% (rs2293152 C/G, rs6503695 C/T, and rs9891119 A/C), representing 24 polymorphicsites of the STAT3 (r2 > 0.8). We observed a significant association between mtDNA/nDNAratio and both rs6503695 and rs9891119, adjusted by age and homeostasis modelassessment index. The proportion of the total variance of the mtDNA/nDNA ratioaccounted for by the rs6503695 and rs9891119 genotypes was 4.7% and 6.53%,respectively. Common variation in the STAT3 may influence mtDNA copy number