Methylation at CpG sites related to growth differentiation factor-15 was not prospectively associated with cardiovascular death in discordant monozygotic twins.

Methylation at CpG sites related to growth differentiation factor-15 was not prospectively associated with cardiovascular death in discordant monozygotic twins.
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DOI:
10.1038/s41598-022-08369-9
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发表时间:
2022-03-15
期刊:
影响因子:
4.6
通讯作者:
Dai J
Dai J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Moore SS;Mukherji P;Leung M;Vrentas CE;Mwanja MM;Dai J

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心肌梗死患者在四个生长分化因子-15 (GDF-15)相关的CpG位点(cg13033858、cg16936953、cg17150809和cg18608055)甲基化降低。这些部位与心血管疾病(CVD)死亡的关系尚未被研究。因此,我们的目的是评估独立于基因、共享环境和传统心血管疾病危险因素的关联。从1969年开始的国家心肺血液研究所双胞胎研究(NHLBI)中纳入了19对心血管疾病死亡不一致的白人男性同卵双胞胎。截止到2014年12月31日,收集生命状态数据。测试3(1986-87)时,使用Illumina HumanMethylation450头芯片测量褐毛DNA的甲基化。使用主成分分析生成一个代表血液白细胞组成和基线CVD危险因素的评分,以自然杀伤细胞、CD4+ T细胞和Framingham风险评分为主。条件逻辑回归显示,在校正评分前(均p >.05, bootstrapp >.05)和校正评分后(均p b>.05),四个CpG位点的甲基化与CVD死亡无关。cg16936953与评分的联合影响有统计学意义(p < 0.05)。综上所述,cg16936953位点甲基化和评分的共同影响与CVD死亡有潜在的相关性,不受种系和普通环境的影响。NHLBI双胞胎研究的标识符:NCT00005124。
Myocardial infarction patients had decreased methylation at four growth differentiating factor-15 (GDF-15) related CpG sites (cg13033858, cg16936953, cg17150809, and cg18608055). These sites had not been studied for their association with cardiovascular disease (CVD) deaths. Thus, we aimed to assess the associations independent of genes, shared environment, and traditional CVD risk factors. Nineteen white, male, monozygotic twin pairs discordant for CVD deaths were included from the National Heart, Lung and Blood Institute Twin Study (NHLBI) initiated in 1969. Data on vital status was collected through December 31, 2014. Methylation of buffy coat DNA at exam 3 (1986–87) was measured using the Illumina HumanMethylation450 BeadChip. Principal component analysis was used to generate a score representing blood leukocyte composition and baseline CVD risk factors and predominated with natural killer cells, CD4+ T cells, and Framingham risk score. Conditional logistic regression demonstrated that methylation at the four CpG sites was not associated with CVD deaths before (all p > 0.05, bootstrapped p > 0.05) and after adjustment for the score (all p > 0.05). Joint influences of cg16936953 and the score were statistically significant (p < 0.05). In conclusion, joint influences of methylation at the site cg16936953 and the score are prospectively associated with CVD deaths independent of germline and common environment. ClinicalTrials.gov Identifier for NHLBI Twin Study: NCT00005124.
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