AHRR Hypomethylation mediates the association between maternal smoking and metabolic profiles in children

被引:2
|
作者
Vidal, Adriana C. [1 ]
Chandramouli, Shivram A. [2 ]
Marchesoni, Joddy [1 ]
Brown, Nia [1 ]
Liu, Yukun [1 ]
Murphy, Susan K. [3 ]
Maguire, Rachel [1 ]
Wang, Yaxu [1 ]
Abdelmalek, Manal F. [4 ]
Mavis, Alisha M. [5 ]
Bashir, Mustafa R. [6 ]
Jima, Dereje [1 ,7 ]
Skaar, David A. [1 ]
Hoyo, Cathrine [1 ]
Moylan, Cynthia A. [2 ,8 ]
机构
[1] North Carolina State Univ, Ctr Human Hlth & Environm, Dept Biol Sci, Raleigh, NC USA
[2] Duke Univ, Med Ctr, Dept Med, Durham, NC USA
[3] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Sci, Durham, NC USA
[4] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA
[5] Duke Univ, Med Ctr, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Durham, NC USA
[6] Duke Univ, Med Ctr, Dept Radiol, Durham, NC USA
[7] North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA
[8] DUMC, 3913 Duke South,Suite 03107,40 Med Circle Dr, Durham, NC 27710 USA
关键词
ARYL-HYDROCARBON RECEPTOR; DNA METHYLATION; TOBACCO-SMOKE; FATTY LIVER; NEWBORNS; OBESITY; PREGNANCY;
D O I
10.1097/HC9.0000000000000243
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children.Methods: We assessed metabolic dysfunction using liver fat content (LFC), serum, and clinical data in children aged 7-12 years (n=78) followed since birth. Maternal smoking was self-reported at 12 weeks gestation. Methylation was measured by means of pyrosequencing at 3 sequential CpG sites, including cg05575921, at birth and at ages 7-12. Regression models were used to evaluate whether AHRR methylation mediated the association between maternal smoking and child metabolic dysfunction.Results: Average AHRR methylation at birth was significantly higher among children of nonsmoking mothers compared with children of mothers who smoked (69.8% +/- 4.4% vs. 63.5% +/- 5.5, p=0.0006). AHRR hypomethylation at birth was associated with higher liver fat content (p=0.01), triglycerides (p=0.01), and alanine aminotransferase levels (p=0.03), and lower HDL cholesterol (p=0.01) in childhood. AHRR hypomethylation significantly mediated associations between maternal smoking and liver fat content (indirect effect=0.213, p=0.018), triglycerides (indirect effect=0.297, p=0.044), and HDL cholesterol (indirect effect = -0.413, p=0.007). AHRR methylation in childhood (n=78) was no longer significantly associated with prenatal smoke exposure or child metabolic parameters (p>0.05).Conclusions: AHRR hypomethylation significantly mediates the association between prenatal tobacco smoke exposure and features of childhood metabolic dysfunction, despite the lack of persistent hypomethylation of AHRR into childhood. Further studies are needed to replicate these findings and to explore their causal and long-term significance.
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页数:9
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