Telomere length analysis on leukocytes derived from patients with Huntington Disease

• Published in: Mechanisms of ageing and development Vol. 185; p. 111189
• Main Authors: PerezGrovas-Saltijeral, Adriana, Ochoa-Morales, Adriana, Miranda-Duarte, Antonio, Martínez-Ruano, Leticia, Jara-Prado, Aurelio, Camacho-Molina, Alejandra, Hidalgo-Bravo, Alberto
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2020
• Subjects: Asymptomatic Diseases; Biomarkers; Cellular Senescence; Correlation of Data; DNA Damage; Female; Humans; Huntingtin Protein - genetics; Huntington disease; Huntington Disease - diagnosis; Huntington Disease - genetics; Huntington Disease - metabolism; Male; Middle Aged; Mitochondria; Neurodegenerative disease; Oxidative Stress; Symptom Assessment - methods; Telomere length; Telomere Shortening; Trinucleotide Repeat Expansion; Trinucleotide repeats; Trinucleotide repeats; Oxidative stress; Neurodegenerative disease; Mitochondria; Telomere length; Huntington disease
• ISSN: 0047-6374; 1872-6216; 1872-6216
• DOI: 10.1016/j.mad.2019.111189

•Analysis of relative telomere length in Huntington disease patients.•Difference between medians of relative telomere length in the three study groups.•No correlation between relative telomere length and age in the three study groups.•Potential association of telomere shortening with Huntington Disease development. Huntington´s disease (HD) is a neurodegenerative disorder characterized by neuropsychiatric, motor and cognitive manifestations. It is caused by expansion of the trinucleotide CAG on HTT. The molecular bases are not completely understood, DNA damage, such as double and single strand breaks and oxidative stress (OS) have been implicated. At telomeres, DNA breaks are less efficiently repaired. Double strand breaks evoke the break induced replication (BIR) mechanism. BIR, plus inefficient repair can produce telomere shortening and cellular senescence. Our aim was to investigate the correlation between leukocyte relative telomeric length (RTL) and HD. 206 samples were analyzed, 71 patients with molecular diagnosis and symptomatology (HD), 29 individuals with positive molecular test but asymptomatic (PP) and 106 healthy individuals (NP). We found a significant difference in RTL between HD patients compared with both, PP and NP, independently of subjects’ age. Here we present evidence supporting an association between telomere shortening and HD. Telomere shortening could be related to DNA damage caused by ROS and defective DNA repair mechanism. Both events have been probed to occur in the presence of a mutant Huntingtin. This study contributes with current evidence suggesting a potential role of telomere shortening as HD biomarker.