Novel DNA Methylation Sites Influence Expression in Relation to Smoking
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Novel DNA Methylation Sites Influence Expression in Relation to Smoking. / Haase, Tina; Müller, Christian; Krause, Julia; Röthemeier, Caroline; Stenzig, Justus; Kunze, Sonja; Waldenberger, Melanie; Münzel, Thomas; Pfeiffer, Norbert; Wild, Philipp S; Michal, Matthias; Marini, Federico; Karakas, Mahir; Lackner, Karl J; Blankenberg, Stefan; Zeller, Tanja.
In: BIOMOLECULES, Vol. 8, No. 3, 20.08.2018, p. E74.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Novel DNA Methylation Sites Influence Expression in Relation to Smoking
AU - Haase, Tina
AU - Müller, Christian
AU - Krause, Julia
AU - Röthemeier, Caroline
AU - Stenzig, Justus
AU - Kunze, Sonja
AU - Waldenberger, Melanie
AU - Münzel, Thomas
AU - Pfeiffer, Norbert
AU - Wild, Philipp S
AU - Michal, Matthias
AU - Marini, Federico
AU - Karakas, Mahir
AU - Lackner, Karl J
AU - Blankenberg, Stefan
AU - Zeller, Tanja
PY - 2018/8/20
Y1 - 2018/8/20
N2 - Smoking is a major risk factor for cardiovascular diseases and has been implicated in the regulation of the G protein-coupled receptor 15 (GPR15) by affecting CpG methylation. The G protein-coupled receptor 15 is involved in angiogenesis and inflammation. An effect on GPR15 gene regulation has been shown for the CpG site CpG3.98251294. We aimed to analyze the effect of smoking on GPR15 expression and methylation sites spanning the GPR15 locus. DNA methylation of nine GPR15 CpG sites was measured in leukocytes from 1291 population-based individuals using the EpiTYPER. Monocytic GPR15 expression was measured by qPCR at baseline and five-years follow up. GPR15 gene expression was upregulated in smokers (beta (ß) = -2.699, p-value (p) = 1.02 × 10-77) and strongly correlated with smoking exposure (ß = -0.063, p = 2.95 × 10-34). Smoking cessation within five years reduced GPR15 expression about 19% (p = 9.65 × 10-5) with decreasing GPR15 expression over time (ß = 0.031, p = 3.81 × 10-6). Additionally, three novel CpG sites within GPR15 affected by smoking were identified. For CpG3.98251047, DNA methylation increased steadily after smoking cessation (ß = 0.123, p = 1.67 × 10-3) and strongly correlated with changes in GPR15 expression (ß = 0.036, p = 4.86 × 10-5). Three novel GPR15 CpG sites were identified in relation to smoking and GPR15 expression. Our results provide novel insights in the regulation of GPR15, which possibly linked smoking to inflammation and disease progression.
AB - Smoking is a major risk factor for cardiovascular diseases and has been implicated in the regulation of the G protein-coupled receptor 15 (GPR15) by affecting CpG methylation. The G protein-coupled receptor 15 is involved in angiogenesis and inflammation. An effect on GPR15 gene regulation has been shown for the CpG site CpG3.98251294. We aimed to analyze the effect of smoking on GPR15 expression and methylation sites spanning the GPR15 locus. DNA methylation of nine GPR15 CpG sites was measured in leukocytes from 1291 population-based individuals using the EpiTYPER. Monocytic GPR15 expression was measured by qPCR at baseline and five-years follow up. GPR15 gene expression was upregulated in smokers (beta (ß) = -2.699, p-value (p) = 1.02 × 10-77) and strongly correlated with smoking exposure (ß = -0.063, p = 2.95 × 10-34). Smoking cessation within five years reduced GPR15 expression about 19% (p = 9.65 × 10-5) with decreasing GPR15 expression over time (ß = 0.031, p = 3.81 × 10-6). Additionally, three novel CpG sites within GPR15 affected by smoking were identified. For CpG3.98251047, DNA methylation increased steadily after smoking cessation (ß = 0.123, p = 1.67 × 10-3) and strongly correlated with changes in GPR15 expression (ß = 0.036, p = 4.86 × 10-5). Three novel GPR15 CpG sites were identified in relation to smoking and GPR15 expression. Our results provide novel insights in the regulation of GPR15, which possibly linked smoking to inflammation and disease progression.
KW - Journal Article
U2 - 10.3390/biom8030074
DO - 10.3390/biom8030074
M3 - SCORING: Journal article
C2 - 30127295
VL - 8
SP - E74
JO - BIOMOLECULES
JF - BIOMOLECULES
SN - 2218-273X
IS - 3
ER -