A16 Understanding the association between mitochondrial DNA copy number and telomere length in huntington’s disease patients

Abstract

Background Huntington’s disease (HD) is a progressive adult-onset neurodegenerative disorder, caused by pathogenic instability of CAG repeats in exon 1 of the HTT gene. Various subcellular structures and their function are known to be impaired, perhaps due to htt poly Q aggregates. Mitochondrial dysfunction and Telomeres shortening are among them. Aim To study the relative telomere length (RTL) and relative mitochondrial DNA (mtDNA) copy number in HD patients, as compared to controls; and the relationship between them. Methodology HD patients (N = 159) and healthy controls (N = 127) were studied. Relative mtDNA copy number was assessed by comparing the mitochondrial gene ND1 to a single copy nuclear gene PK1. And for the RTL, was computed by measuring telomere repeats, and the single-copy gene, 36B4 using specific primers. 2-ΔΔCt was calculated for each experiment as the measure of relative mtDNA copy number and RTL. Results The RTL was significantly lower in HD compared to controls (P = 0.042), whereas relative mtDNA copy number did not differ between HD and controls (P = 0.441). The relative mtDNA copy number showed significant positive association with RTL in controls (r = 0.197, P = 0.025), but not in HD patients (r = 0.057, P = 0.469). Conclusion Telomere length was attenuated in those with HD. The mitochondrial copy number did not show any difference. There was a significant association between RTL and relative mtDNA copy number in controls, but not in HD. Understanding the molecular mechanisms underlying telomere-mt DNA association is important.