Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD. We examined three polymorphisms of the TERT gene (VNTR MNS16A, rs2853691, rs33954691) and three polymorphisms of the TERC gene (rs12696304, rs3772190, rs16847897) in a sample of 220 AD patients and 146 controls. MNS16A LL genotype was found to be associated with an increased risk of AD only in males [interaction term adjusted OR=3.55 (95% CI 1.2-10.2)]. The three TERC single nucleotide polymorphisms are in strict linkage disequilibrium and their genotype combinations influenced the age at AD onset (AAO). The combined genotype GG-TT-CC was associated with a mean AAO six years lower (70.5±6.7) than that associated with the other genotype combinations (76.04±6.7, p=0.01). The fact that the MNS16 L allele has been reported to lower TERT expression, and that the TERC alleles G, T, C (rs12696304, rs3772190, rs16847897 in this order have been repeatedly found associated with shorter LTL, seems to corroborate the hypothesis of a role of telomere length and telomerase in AD susceptibility.

Common variants of human TERT and TERC genes and susceptibility to sporadic Alzheimers disease / Scarabino, D.; Broggio, E.; Gambina, G.; Pelliccia, Franca; Corbo, Rosa Maria. - In: EXPERIMENTAL GERONTOLOGY. - ISSN 0531-5565. - STAMPA. - 88:(2017), pp. 19-24. [10.1016/j.exger.2016.12.017]

Common variants of human TERT and TERC genes and susceptibility to sporadic Alzheimers disease

PELLICCIA, Franca;CORBO, Rosa Maria
2017

Abstract

Studies investigating telomere length in association with cognitive decline, dementia, and sporadic Alzheimer's disease (AD) have frequently found shorter telomeres to be associated with the development of AD and telomerase expression with pathological processes in AD. Human telomerase is constituted by two components: the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). Genetic variation at the two loci has been investigated in relation to telomere length, longevity, and common diseases of advanced age, but not in relation to AD. We examined three polymorphisms of the TERT gene (VNTR MNS16A, rs2853691, rs33954691) and three polymorphisms of the TERC gene (rs12696304, rs3772190, rs16847897) in a sample of 220 AD patients and 146 controls. MNS16A LL genotype was found to be associated with an increased risk of AD only in males [interaction term adjusted OR=3.55 (95% CI 1.2-10.2)]. The three TERC single nucleotide polymorphisms are in strict linkage disequilibrium and their genotype combinations influenced the age at AD onset (AAO). The combined genotype GG-TT-CC was associated with a mean AAO six years lower (70.5±6.7) than that associated with the other genotype combinations (76.04±6.7, p=0.01). The fact that the MNS16 L allele has been reported to lower TERT expression, and that the TERC alleles G, T, C (rs12696304, rs3772190, rs16847897 in this order have been repeatedly found associated with shorter LTL, seems to corroborate the hypothesis of a role of telomere length and telomerase in AD susceptibility.
2017
Age at disease onset; Alzheimer's disease susceptibility; TERC genotypes; TERT genotypes; Biochemistry; Aging; Molecular Biology; Genetics; Endocrinology; Cell Biology
01 Pubblicazione su rivista::01a Articolo in rivista
Common variants of human TERT and TERC genes and susceptibility to sporadic Alzheimers disease / Scarabino, D.; Broggio, E.; Gambina, G.; Pelliccia, Franca; Corbo, Rosa Maria. - In: EXPERIMENTAL GERONTOLOGY. - ISSN 0531-5565. - STAMPA. - 88:(2017), pp. 19-24. [10.1016/j.exger.2016.12.017]
File allegati a questo prodotto
File Dimensione Formato  
Scarabino_Common_2017.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 313.5 kB
Formato Adobe PDF
313.5 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/947921
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 23
social impact