Poster Session 4
Category: Hypertension
Poster Session 4
Mudit Vaid, MS, PhD
Department of Obstetrics and Gynecology, University of Alabama at Birmingham
Birmingham, Alabama, United States
Amit Patki, MS
Department of Biostatistics, University of Alabama at Birmingham
Birmingham, Alabama, United States
Jeff M. Szychowski, PhD
Associate Professor
Department of Biostatistics, University of Alabama at Birmingham
Birmingham, Alabama, United States
Hemant Tiwari, MS, PhD
Department of Biostatistics, University of Alabama at Birmingham
Birmingham, Alabama, United States
Alana Jones, MD, PhD
Department of Epidemiology, University of Alabama at Birmingham
Birmingham, Alabama, United States
Javier Velez, MSPH
Heersink School of Medicine, University of Alabama at Birmingham
Birmingham, Alabama, United States
Ryan Ryan Irvin, MS, PhD
Department of Epidemiology, University of Alabama at Birmingham
Birmingham, Alabama, United States
Alan T. Tita, MD, MPH, PhD (he/him/his)
Assoc. Dean for Global & Women’s Health; Chair & Director, Mary Heersink Inst. of Global Health
Center for Research in Women’s Health, University of Alabama at Birmingham
Birmingham, Alabama, United States
Akila Subramaniam, MD, MPH (she/her/hers)
Professor
Center for Research in Women’s Health, University of Alabama at Birmingham
Birmingham, Alabama, United States
.jpeg.jpg "Bertha A. Hidalgo, MPH, PhD photo")
Bertha A. Hidalgo, MPH, PhD
Associate Professor & Associate Dean
Department of Epidemiology, University of Alabama at Birmingham
Birmingham, Alabama, United States
Smoking-associated DNA methylation is well-characterized in the general population, but data in pregnancy are sparse. Given the increased risk of hypertensive disorders of pregnancy (HDP) in women with chronic hypertension (CHTN), and paradoxically decreased rates of HDP in smokers, we aimed to investigate smoking-induced epigenetic changes in gravidas with CHTN.
Study Design:
We performed a secondary analysis of the CHAP Epigenetics Study. Blood samples collected at time of randomization from the original CHAP trial comparing antihypertensive treatment vs. non-treatment in pregnant women with mild CHTN at < 23 weeks’ gestation were utilized. Baseline genomic DNA was profiled for methylation levels using the Illumina EPIC v2.0 array. Participants were categorized as smokers or non-smokers based on self-report. Epigenome-wide association study (EWAS) analyses were performed using linear regression models adjusted for age, treatment group, ancestry, cell proportions, BMI, and alcohol use to identify cytosine-phosphate-guanine (CpGs) sites associated with smoking. Differentially methylated regions (DMRs) for smoking were also identified using the coMethDMR package in R.
Results:
1,392 individuals [157 (11.3%) smokers and 1235 non-smokers] were analyzed (Table 1). We identified 149 CpG sites significantly associated with smoking (p< 4.91×10⁻⁸). Of these, 84 mapped to 55 genes enriched in known smoking-related loci (AHRR, GFI1, MYO1G, PRSS23); 99 (~66%) were previously reported, while 50 were novel (Table 2). Additionally, we identified 22 smoking-related DMRs (FDR< 0.009), each comprising 3–10 CpGs in close genomic proximity. Four CpGs from the DMR analysis overlapped with the EWAS (cg12303084, cg05445320, cg11427534, cg09662411), indicating greater biological relevance.
Conclusion:
Smoking in pregnant women with mild CHTN is associated with distinct methylation signatures. These findings represent potential biomarkers to understand the relationships between smoking, CHTN, and HDP and may inform future interventions for mitigating adverse pregnancy outcomes in this high-risk group.