Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women
Shannon L Gillespie1, Jeremy L Neal, Lisa M Christian
1Shannon L. Gillespie, PhD, MS, RN, is Postdoctoral Researcher, College of Nursing, The Ohio State University, Columbus. Jeremy L. Neal, PhD, CNM, RN, is Assistant Professor, School of Nursing, Vanderbilt University, Nashville, Tennessee. Lisa M. Christian, PhD, is Associate Professor, Department of Psychiatry and Behavioral Health, The Institute for Behavioral Medicine Research, and Department of Obstetrics and Gynecology, Wexner Medical Center, Department of Psychology, The Ohio State University, Columbus. Laura A. Szalacha, EdD, is Professor, College of Nursing, University of Arizona, Tucson. Donna O. McCarthy, PhD, RN, FAAN, is Professor, Marquette University, Milwaukee, Wisconsin. Pamela J. Salsberry, PhD, RN, FAAN, is Professor, Department of Health Behavior and Health Promotion, College of Public Health, The Ohio State University, Columbus.
African American women with the IL1RN gene GG genotype may experience earlier birth due to reduced inhibition of interleukin-1 beta (IL-1β) production, impacting inflammatory responses and newborn health.
Area of Science:
- Reproductive biology
- Immunology
- Genetics
Background:
- Timing of birth is crucial for newborn health.
- African American women face higher risks of preterm birth, often linked to inflammation.
- Interleukin-1 receptor antagonist (IL-1RN) gene variants are associated with early birth, but pathways remain unclear.
Purpose of the Study:
- To investigate the association between an IL1RN gene variant and birth timing in African American women.
- To determine if this association is mediated by IL-1Ra production or linked to IL-1β production.
- To explore inflammatory pathway differences in relation to birth timing within this demographic.
Main Methods:
- A prospective cohort study of 89 African American women with uncomplicated pregnancies.
- Genotyping of IL1RN single-nucleotide polymorphism (SNP) rs2637988.
- Quantification of lipopolysaccharide-stimulated IL-1Ra and IL-1β production; birth timing determined by medical records.
Main Results:
- Women with the GG genotype had earlier births compared to AA/AG genotypes (p=0.04).
- No mediation effect of IL1RN SNP rs2637988 on birth timing via IL-1Ra production was found.
- GG genotype was linked to reduced IL-1β inhibition (p=0.03), and higher IL-1β was marginally associated with earlier birth (p=0.05).
Conclusions:
- The GG genotype of IL1RN may increase early birth risk due to impaired IL-1β inhibition, potentially initiating inflammatory responses.
- Further research into inflammatory pathways among African American women is crucial for identifying risk markers and interventions for early birth.
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