Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on G×E interactions and pathogenic pathways

Abstract

Preterm delivery (PTD, <37 weeks of gestation) is a significant clinical and public health problem. Previously, we reported that maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 synergistically increase the risk of low birth weight. This study investigates the relationship between maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 with preterm delivery (PTD) as a whole and preterm subgroups. This case-control study included 1,749 multi-ethnic mothers (571 with PTD and 1,178 controls) enrolled at Boston Medical Center. After adjusting covariates, regression analyses were performed to identify individual and joint associations of maternal smoking, two functional variants of CYP1A1 and GSTT1 with PTD. We observed a moderate effect of maternal smoking on PTD (OR = 1.6; 95% CI: 1.1-2.2). We found that compared to non-smoking mothers with low-risk genotypes, there was a significant joint association of maternal smoking, CYP1A1 (Aa/aa) and GSTT1 (absent) genotypes with gestational age (beta = -3.37; SE = 0.86; P = 9 x 10(-5)) and with PTD (OR = 5.8; 95% CI: 2.0-21.1), respectively. Such joint association was particularly strong in certain preterm subgroups, including spontaneous PTD (OR = 8.3; 95% CI: 2.7-30.6), PTD < 32 weeks (OR = 11.1; 95% CI: 2.9-47.7), and PTD accompanied by histologic chorioamnionitis (OR = 15.6; 95% CI: 4.1-76.7). Similar patterns were observed across ethnic groups. Taken together, maternal smoking significantly increased the risk of PTD among women with high-risk CYP1A1 and GSTT1 genotypes. Such joint associations were strongest among PTD accompanied by histologic chorioamnionitis.

Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life

“…The initial recruitment and follow-up have been previously described. [46][47][48] This report included 105 Black children (59 males and 46 females), who were singleton, full-term births and whose cord blood and venous blood were collected at birth and within the first two years of life, respectively. Written informed consents were obtained from all participants in this study.…”

Maternal Pre-Pregnancy Obesity and Recurrent Wheezing in Early Childhood

“…This approach has been used in large hospital-based preterm studies and in our ongoing funded preterm studies. 29,33,34 Subjects were categorized as having preterm delivery if they were <37 weeks gestation at delivery. Infant race/ethnicity was based on self-report provided by the mother and categorized as nonhispanic black, nonhispanic white, hispanic, or other.…”

425: Maternal tobacco use modestly alters correlated epigenome wide placental DNA methylation and gene expression

“…Quantification of signal intensity after allele-specific priming and single base extension of fluorescently labeled ddNTPs allows for intensity While initial clues about the potential genetic, epigenetic and physiologic mechanisms involved in these observations have been reported, these have yet to be fully characterized. [13][14][15][16][17][18][19][20][21] Epigenetic variation of DNA, particularly methyl group modifications to cytosine bases adjacent to guanines (CpG dinucleotides) represent an important form of epigenomic variation during critical windows in development. 2,4 Loosely ascribed changes in the levels of DNA methylation are associated with maternal smoking behavior.…”