Association between Genetic Variants in DNA and Histone Methylation and Telomere Length

Hdl Handle:
http://hdl.handle.net/10675.2/806
Title:
Association between Genetic Variants in DNA and Histone Methylation and Telomere Length
Authors:
Kim, Sangmi; Parks, Christine G.; Xu, Zongli; Carswell, Gleta; DeRoo, Lisa A.; Sandler, Dale P.; Taylor, Jack A.
Abstract:
Telomere length, a biomarker of aging and age-related diseases, exhibits wide variation between individuals. Common genetic variation may explain some of the individual differences in telomere length. To date, however, only a few genetic variants have been identified in the previous genome-wide association studies. As emerging data suggest epigenetic regulation of telomere length, we investigated 72 single nucleotide polymorphisms (SNPs) in 46 genes that involve DNA and histone methylation as well as telomerase and telomere-binding proteins and DNA damage response. Genotyping and quantification of telomere length were performed in blood samples from 989 non-Hispanic white participants of the Sister Study, a prospective cohort of women aged 35–74 years. The association of each SNP with logarithmically-transformed relative telomere length was estimated using multivariate linear regression. Six SNPs were associated with relative telomere length in blood cells with p-values<0.05 (uncorrected for multiple comparisons). The minor alleles of BHMT rs3733890 G>A (p = 0.041), MTRR rs2966952 C>T (p = 0.002) and EHMT2 rs558702 G>A (p = 0.008) were associated with shorter telomeres, while minor alleles of ATM rs1801516 G>A (p = 0.031), MTR rs1805087 A>G (p = 0.038) and PRMT8 rs12299470 G>A (p = 0.019) were associated with longer telomeres. Five of these SNPs are located in genes coding for proteins involved in DNA and histone methylation. Our results are consistent with recent findings that chromatin structure is epigenetically regulated and may influence the genomic integrity of telomeric region and telomere length maintenance. Larger studies with greater coverage of the genes implicated in DNA methylation and histone modifications are warranted to replicate these findings.
Citation:
PLoS One. 2012 Jul 11; 7(7):e40504
Issue Date:
11-Jul-2012
URI:
http://hdl.handle.net/10675.2/806
DOI:
10.1371/journal.pone.0040504
PubMed ID:
22792358
PubMed Central ID:
PMC3394714
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Medicine Faculty: Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorKim, Sangmien_US
dc.contributor.authorParks, Christine G.en_US
dc.contributor.authorXu, Zonglien_US
dc.contributor.authorCarswell, Gletaen_US
dc.contributor.authorDeRoo, Lisa A.en_US
dc.contributor.authorSandler, Dale P.en_US
dc.contributor.authorTaylor, Jack A.en_US
dc.date.accessioned2012-10-26T20:30:47Z-
dc.date.available2012-10-26T20:30:47Z-
dc.date.issued2012-07-11en_US
dc.identifier.citationPLoS One. 2012 Jul 11; 7(7):e40504en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22792358en_US
dc.identifier.doi10.1371/journal.pone.0040504en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/806-
dc.description.abstractTelomere length, a biomarker of aging and age-related diseases, exhibits wide variation between individuals. Common genetic variation may explain some of the individual differences in telomere length. To date, however, only a few genetic variants have been identified in the previous genome-wide association studies. As emerging data suggest epigenetic regulation of telomere length, we investigated 72 single nucleotide polymorphisms (SNPs) in 46 genes that involve DNA and histone methylation as well as telomerase and telomere-binding proteins and DNA damage response. Genotyping and quantification of telomere length were performed in blood samples from 989 non-Hispanic white participants of the Sister Study, a prospective cohort of women aged 35–74 years. The association of each SNP with logarithmically-transformed relative telomere length was estimated using multivariate linear regression. Six SNPs were associated with relative telomere length in blood cells with p-values<0.05 (uncorrected for multiple comparisons). The minor alleles of BHMT rs3733890 G>A (p = 0.041), MTRR rs2966952 C>T (p = 0.002) and EHMT2 rs558702 G>A (p = 0.008) were associated with shorter telomeres, while minor alleles of ATM rs1801516 G>A (p = 0.031), MTR rs1805087 A>G (p = 0.038) and PRMT8 rs12299470 G>A (p = 0.019) were associated with longer telomeres. Five of these SNPs are located in genes coding for proteins involved in DNA and histone methylation. Our results are consistent with recent findings that chromatin structure is epigenetically regulated and may influence the genomic integrity of telomeric region and telomere length maintenance. Larger studies with greater coverage of the genes implicated in DNA methylation and histone modifications are warranted to replicate these findings.en_US
dc.rightsThis is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectGeneticsen_US
dc.subjectEpigeneticsen_US
dc.subjectHistone Modificationen_US
dc.subjectGene Expressionen_US
dc.subjectHistone Modificationen_US
dc.subjectGenomicsen_US
dc.subjectChromosome Biologyen_US
dc.subjectTelomeresen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectChromosome Biologyen_US
dc.subjectTelomeresen_US
dc.subjectGene Expressionen_US
dc.subjectHistone Modificationen_US
dc.subjectMedicineen_US
dc.subjectEpidemiologyen_US
dc.subjectBiomarker Epidemiologyen_US
dc.subjectCancer Epidemiologyen_US
dc.subjectEpidemiology of Agingen_US
dc.subjectGenetic Epidemiologyen_US
dc.subjectMolecular Epidemiologyen_US
dc.titleAssociation between Genetic Variants in DNA and Histone Methylation and Telomere Lengthen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3394714en_US
dc.contributor.corporatenameDepartment of Medicine-

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