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Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study

One of the markers of aging is lymphocyte telomere length (LTL), which is affected by genetic constitution of the organism and environmental conditions, such as development and diseases, including diabetes. The relationship of the later seems to be bilateral. The enzyme responsible for the maintenan...

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Autores principales: Gutmajster, Ewa, Chudek, Jerzy, Augusciak-Duma, Aleksandra, Szwed, Malgorzata, Szybalska, Aleksandra, Mossakowska, Malgorzata, Puzianowska-Kuznicka, Monika, Wiecek, Andrzej, Sieron, Aleksander L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060992/
https://www.ncbi.nlm.nih.gov/pubmed/29938393
http://dx.doi.org/10.1007/s13353-018-0450-9
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author Gutmajster, Ewa
Chudek, Jerzy
Augusciak-Duma, Aleksandra
Szwed, Malgorzata
Szybalska, Aleksandra
Mossakowska, Malgorzata
Puzianowska-Kuznicka, Monika
Wiecek, Andrzej
Sieron, Aleksander L.
author_facet Gutmajster, Ewa
Chudek, Jerzy
Augusciak-Duma, Aleksandra
Szwed, Malgorzata
Szybalska, Aleksandra
Mossakowska, Malgorzata
Puzianowska-Kuznicka, Monika
Wiecek, Andrzej
Sieron, Aleksander L.
author_sort Gutmajster, Ewa
collection PubMed
description One of the markers of aging is lymphocyte telomere length (LTL), which is affected by genetic constitution of the organism and environmental conditions, such as development and diseases, including diabetes. The relationship of the later seems to be bilateral. The enzyme responsible for the maintenance of telomere length is a subunit of telomerase—telomerase reverse transcriptase (TERT). The aims of the present study were to (1) determine the influence of the TERT promoter sequence SNP variants on relative telomere length (RTL) in an elderly Polish population and (2) explore the potential associations of the SNPs with the type 2 diabetes mellitus (T2DM) in the obese individuals. Two highly homogenous subgroups of PolSenior participants were investigated, the first constituted 70 relatively healthy respondents and the second 70 individuals with T2DM. Telomere length ratio (T/S value) was measured; 1.5 kb part upstream of the transcription start site of the TERT promoter was sequenced, and the frequencies of polymorphisms were calculated and compared against analysed data. Low-frequency SNPs were evaluated but excluded from further comparative analyses to RTL and glucose metabolism markers. No significant difference in telomere length was found between the two studied subgroups. Univariate statistical analyses showed only a weak association of environmental or genetic factors altering this marker of aging. Approximate frequency of four SNPs in TERT promoter sequence was assessed in Polish population aged 65–95 years, but three of them (rs2735940, rs7712562 and rs2853669) were selected for further analyses. The SNP selection was based on their minor allele frequencies in general population and on published data. The univariate analysis has revealed that carriers of CC SNP (rs2853669) have had the shortest RTL in the T2DM group. Multivariate analysis has also revealed that the genetic effect of TERT promoter CC SNP was strengthened by the incidence of T2DM. The additional variation in RTL in paired groups indicates that in addition to T2DM and genetics, there are other factors contributing to development of the age-related diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13353-018-0450-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-60609922018-08-09 Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study Gutmajster, Ewa Chudek, Jerzy Augusciak-Duma, Aleksandra Szwed, Malgorzata Szybalska, Aleksandra Mossakowska, Malgorzata Puzianowska-Kuznicka, Monika Wiecek, Andrzej Sieron, Aleksander L. J Appl Genet Human Genetics • Original Paper One of the markers of aging is lymphocyte telomere length (LTL), which is affected by genetic constitution of the organism and environmental conditions, such as development and diseases, including diabetes. The relationship of the later seems to be bilateral. The enzyme responsible for the maintenance of telomere length is a subunit of telomerase—telomerase reverse transcriptase (TERT). The aims of the present study were to (1) determine the influence of the TERT promoter sequence SNP variants on relative telomere length (RTL) in an elderly Polish population and (2) explore the potential associations of the SNPs with the type 2 diabetes mellitus (T2DM) in the obese individuals. Two highly homogenous subgroups of PolSenior participants were investigated, the first constituted 70 relatively healthy respondents and the second 70 individuals with T2DM. Telomere length ratio (T/S value) was measured; 1.5 kb part upstream of the transcription start site of the TERT promoter was sequenced, and the frequencies of polymorphisms were calculated and compared against analysed data. Low-frequency SNPs were evaluated but excluded from further comparative analyses to RTL and glucose metabolism markers. No significant difference in telomere length was found between the two studied subgroups. Univariate statistical analyses showed only a weak association of environmental or genetic factors altering this marker of aging. Approximate frequency of four SNPs in TERT promoter sequence was assessed in Polish population aged 65–95 years, but three of them (rs2735940, rs7712562 and rs2853669) were selected for further analyses. The SNP selection was based on their minor allele frequencies in general population and on published data. The univariate analysis has revealed that carriers of CC SNP (rs2853669) have had the shortest RTL in the T2DM group. Multivariate analysis has also revealed that the genetic effect of TERT promoter CC SNP was strengthened by the incidence of T2DM. The additional variation in RTL in paired groups indicates that in addition to T2DM and genetics, there are other factors contributing to development of the age-related diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13353-018-0450-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-06-25 2018 /pmc/articles/PMC6060992/ /pubmed/29938393 http://dx.doi.org/10.1007/s13353-018-0450-9 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Human Genetics • Original Paper
Gutmajster, Ewa
Chudek, Jerzy
Augusciak-Duma, Aleksandra
Szwed, Malgorzata
Szybalska, Aleksandra
Mossakowska, Malgorzata
Puzianowska-Kuznicka, Monika
Wiecek, Andrzej
Sieron, Aleksander L.
Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study
title Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study
title_full Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study
title_fullStr Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study
title_full_unstemmed Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study
title_short Possible association of the TERT promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly Polish population: results from the national PolSenior study
title_sort possible association of the tert promoter polymorphisms rs2735940, rs7712562 and rs2853669 with diabetes mellitus in obese elderly polish population: results from the national polsenior study
topic Human Genetics • Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060992/
https://www.ncbi.nlm.nih.gov/pubmed/29938393
http://dx.doi.org/10.1007/s13353-018-0450-9
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