Common variants of human TERT and TERC genes and susceptibility to sporadic Alzheimer's disease
| Autor: | Rosa Maria Corbo, Daniela Scarabino, Giuseppe Gambina, Elisabetta Broggio, Franca Pelliccia |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Aging Linkage disequilibrium Telomerase Longevity Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Biochemistry 03 medical and health sciences Telomerase RNA component Endocrinology Alzheimer Disease Genotype Genetics Humans Genetic Predisposition to Disease Telomerase reverse transcriptase Age of Onset Cognitive decline Molecular Biology Telomere Shortening Aged Aged 80 and over TERC genotypes TERT genotypes Alzheimer's disease susceptibility Age at disease onset Cell Biology Telomere Logistic Models 030104 developmental biology Italy Linear Models RNA Female Age at disease onset Alzheimer's disease susceptibility TERC genotypes TERT genotypes |
| Zdroj: | Experimental gerontology 88 (2017): 19–24. doi:10.1016/j.exger.2016.12.017 info:cnr-pdr/source/autori:D. Scarabino a, E. Broggiob, G. Gambina b, F. Pelliccia c, R.M. Corbo c/titolo:Common variants of human TERT and TERC genes and susceptibility to sporadic Alzheimer's disease./doi:10.1016%2Fj.exger.2016.12.017/rivista:Experimental gerontology/anno:2017/pagina_da:19/pagina_a:24/intervallo_pagine:19–24/volume:88 |
| DOI: | 10.1016/j.exger.2016.12.017 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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