Genetic Contributions to Disparities in Preterm Birth

Abstract

Ethnic disparity in preterm delivery between African Americans and European Americans has existed for decades, and is likely the consequence of multiple factors, including socioeconomic status, access to care, environment, and genetics. This review summarizes existing information on genetic variation and its association with preterm birth in African Americans. Candidate gene-based association studies, in which investigators have evaluated particular genes selected primarily because of their potential roles in the process of normal and pathological parturition, provide evidence that genetic contributions from both mother and fetus account for some of the disparity in preterm births. To date, most attention has been focused on genetic variation in pro- and anti-inflammatory cytokine genes and their respective receptors. These genes, particularly the pro-inflammatory cytokine genes and their receptors, are linked to matrix metabolism since these cytokines increase expression of matrix degrading metalloproteinases. However, the role that genetic variants that are different between populations play in preterm birth cannot yet be quantified. Future studies based on genome wide association or admixture mapping may reveal other genes that contribute to disparity in prematurity.

Synopsis of Preterm Birth Genetic Association Studies: The Preterm Birth Genetics Knowledge Base (PTBGene)

“…Several pathways leading to preterm birth have been outlined, including (1) inflammation, (2) maternal/fetal stress, (3) uterine distension and cervical dysfunction, (4) decidual hemorrhage, and (5) metabolic enzyme variation [5,6]. A modest body of literature has examined the complex genetic contribution to preterm birth [7,8,9], with heritability estimates in the range of 27–36% [10,11]. Several studies have reported associations with single gene variants [12,13,14,15,16,17,18,19,20,21].…”

Anticytokine Therapy in Preterm Labor: Current Knowledge and Future Perspectives

“…Preterm birth has multiple etiologies [2]: there are many maternal or fetal characteristics that have been associated with this disorder, including demographic characteristics, nutritional status such as a low pregnancy body mass index, pregnancy history such as a previous preterm birth and a shorter interpregnancy interval, present pregnancy characteristics such as uterine overdistension due to multiple gestation and polyhydramnios, psychological characteristics and physical abuse, traditional factors or adverse behaviors such as smoking and drinking excess alcohol, as well as routine prepregnancy health promotion [3,4]. Ethnic disparity has also existed, and is likely the consequence of multiple factors, including socioeconomic status and access to public care [5]. The management depends on several variables like gestational age, fetal status and severity of laboratory abnormalities.…”

The Effect of Inflammation on Preterm Birth

“…Furthermore, there is a well-described ethnic difference in the rate of PTB (even when controlling for mother contributing etiologic factors). In 2005, the incidence of preterm delivery among African Americans and European Americans in the U.S. was 18.4% and 11.7%, respectively (Anum et al, 2009). This ethnic disparity in PTB between African Americans and European Americans has been present for decades.…”

“…This ethnic disparity in PTB between African Americans and European Americans has been present for decades. The inequity is likely the consequence of multiple factors, including socioeconomic status, access to care, environment, and differences in genetic background (Anum et al, 2009). …”