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411.
Lindsay M. Reynolds Kurt Lohman Gary S. Pittman R. Graham Barr Gloria C. Chi Joel Kaufman 《Epigenetics》2017,12(12):1092-1100
Alterations in DNA methylation and gene expression in blood leukocytes are potential biomarkers of harm and mediators of the deleterious effects of tobacco exposure. However, methodological issues, including the use of self-reported smoking status and mixed cell types have made previously identified alterations in DNA methylation and gene expression difficult to interpret. In this study, we examined associations of tobacco exposure with DNA methylation and gene expression, utilizing a biomarker of tobacco exposure (urine cotinine) and CD14+ purified monocyte samples from 934 participants of the community-based Multi-Ethnic Study of Atherosclerosis (MESA). Urine cotinine levels were measured using an immunoassay. DNA methylation and gene expression were measured with microarrays. Multivariate linear regression was used to test for associations adjusting for age, sex, race/ethnicity, education, and study site. Urine cotinine levels were associated with methylation of 176 CpGs [false discovery rate (FDR)<0.01]. Four CpGs not previously identified by studies of non-purified blood samples nominally replicated (P value<0.05) with plasma cotinine-associated methylation in 128 independent monocyte samples. Urine cotinine levels associated with expression of 12 genes (FDR<0.01), including increased expression of P2RY6 (Beta ± standard error = 0.078 ± 0.008, P = 1.99 × 10?22), a gene previously identified to be involved in the release of pro-inflammatory cytokines. No cotinine-associated (FDR<0.01) methylation profiles significantly (FDR<0.01) correlated with cotinine-associated (FDR<0.01) gene expression profiles. In conclusion, our findings i) identify potential monocyte-specific smoking-associated methylation patterns and ii) suggest that alterations in methylation may not be a main mechanism regulating gene expression in monocytes in response to cigarette smoking. 相似文献
412.
Abstract Little is known about how grandmothers may influence children's development, although they may frequently assist parents in the raising of their children, especially among low-income families. Data from Welfare, Children, and Families: A Three-City Study were used to explore how preschoolers function academically and psychologically over time based on grandmothers' residential status and level of caretaking responsibility. Longitudinal regression analyses suggest that children who consistently have custodial grandmothers lag behind their peers in the development of their academic achievement, whereas those in multigenerational households consistently have more socioemotional problems over time. However, many of these differences are accounted for by co-occurring family characteristics. Furthermore, children transitioning into the care of custodial grandmothers were found to have positive changes in self-regulation and socioemotional functioning, and those transitioning into multigenerational households had more problems with self-regulation over time. 相似文献