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Alcohol Use During Pregnancy is Associated with Specific Alterations in Micro RNA Levels in Maternal Serum
Author(s) -
Gardiner Amy S.,
Gutierrez Hilda L.,
Luo Li,
Davies Suzy,
Savage Daniel D.,
Bakhireva Ludmila N.,
PerroneBizzozero Nora I.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13026
Subject(s) - pregnancy , rna , alcohol , andrology , obstetrics , medicine , chemistry , biology , genetics , biochemistry , gene
Background Given the challenges of confirming prenatal alcohol exposure ( PAE ) during pregnancy using currently established biomarkers of alcohol consumption, we examined whether serum micro RNA s (mi RNA s) may serve as stable biomarkers for PAE . Alterations in the levels of specific circulating mi RNA s have been associated with various disease states and in animal models of fetal alcohol spectrum disorder. Methods Pregnant women in this prospective study were recruited from substance abuse and general maternity clinics affiliated with the U niversity of N ew M exico. Serum was collected at the time of admission for delivery from 14 subjects who reported ≥1 binge‐drinking episode or ≥3 drinks/wk during pregnancy and 16 subjects who reported abstinence during pregnancy and tested negative for 5 ethanol biomarkers. Total RNA was isolated from serum and used for microarray analysis. Results False discovery rate‐corrected analyses of covariance revealed that 55 mi RNA s were significantly altered between the 2 groups. Hierarchical clustering using only the significantly altered mi RNA s grouped samples into alcohol‐consuming and non‐alcohol‐consuming individuals. Discriminant analysis then identified miRs‐122*, ‐126, ‐216b, ‐221*, ‐3119, ‐3942‐5p, ‐4704‐3p, ‐4743, ‐514‐5p, and ‐602 as the top 10 discriminators between the 2 groups. Ingenuity Pathway Analysis of putative mi RNA targets illustrated that mi RNA s identified in this study are involved in biological pathways that mediate the effects of alcohol, such as brain‐derived neurotrophic factor, ERK 1/2, and PI 3K/ AKT signaling. Conclusions This is the first report of alterations in serum mi RNA expression that are associated with alcohol use during human pregnancy. These results suggest that serum mi RNA s could be useful as biomarkers of alcohol exposure.