Polymorphisms in Inflammatory Genes are Associated with Term Small for Gestational Age and Preeclampsia

Abstract

Problem Inflammatory biomarkers are associated with preeclampsia (PE) and poor fetal growth; however, genetic epidemiologic studies have been limited by reduced gene coverage and the exclusion of African American mothers. Method of study Cases and controls (N = 1646) from a pregnancy cohort were genotyped for 503 tagSNPs in 40 genes related to inflammation. Gene-set analyses were stratified by race and were followed by a single SNP analysis within significant gene sets. Results Gene-level associations were found for IL6 and KLRD1 for term small for gestational age (SGA) among African Americans. LTA/TNF and TBX21 were associated with PE among European Americans. The strongest association was for PE among European Americans for an upstream regulator of TNF with RR = 1.8 (95% CI 1.1–2.7). Conclusion Although previous studies have suggested null associations, increased tagging and stratification by genetic ancestry suggests important associations between IL6 and term SGA for African Americans, and a TNF regulator and PE among European Americans (N = 149).

CD74-Downregulation of Placental Macrophage-Trophoblastic Interactions in Preeclampsia

“…Association studies of polymorphisms in inflammatory genes involved in preeclampsia are controversial. 46 However, further studies to reveal the mechanisms that underlie the transcriptional regulation of CD74 are important.…”

Mid-pregnancy circulating immune biomarkers in women with preeclampsia and normotensive controls

“…Fewer studies have examined TNF-β. Although, TNF-β gene polymorphisms have been found to be associated with preeclampsia among European women [39] and have also been implicated to be associated with preeclampsia in incompatibility models [40]. …”

Maternal Interleukin Genotypes Are Associated With NICU Outcomes Among Low-Birth-Weight Infants

“…The infant's vital signs and lab results used to calculate SNAPPE-II scores are collected within hours of birth, thus this score may reflect the immediately preceding in utero environment. Previous work has identified relationships between IL6 SNPs and SGA infants (Harmon et al, 2014) and preterm birth (Moura et al, 2009; Sugita et al, 2012; Velez, Fortunato, Williams, & Menon, 2008). Interestingly, both Velez, Fortunato, Williams, and Menon (2008) and Harmon et al (2014) uncovered these relationships only among African Americans, an observation that our findings share.…”

“…Previous work has identified relationships between IL6 SNPs and SGA infants (Harmon et al, 2014) and preterm birth (Moura et al, 2009; Sugita et al, 2012; Velez, Fortunato, Williams, & Menon, 2008). Interestingly, both Velez, Fortunato, Williams, and Menon (2008) and Harmon et al (2014) uncovered these relationships only among African Americans, an observation that our findings share. IL-6 is a pleiotropic cytokine that may influence the ability of the placenta to become adequately implanted (Conde-Agudelo, Romero, Kusanovic, & Hassan, 2011), and higher levels of IL-6 are associated with preterm labor (Chaemsaithong et al, 2016).…”

“…SNPs in the promoter region of the IL6 gene influence IL-6 levels (Malarstig, Lindahl, Wallentin, & Siegbahn, 2006), and altered maternal IL-6 production is associated with obstetrical complications, including preterm labor (Chaemsaithong et al, 2016; Lee et al, 2007). Particular maternal genetic variations of IL6 are also associated with spontaneous preterm birth (Moura et al, 2009) and SGA among term infants (Harmon et al, 2014). IL-10 is a regulatory cytokine, and SNPs in the promoter region of the IL10 gene are associated with IL-10 levels (Capasso et al, 2007; Lowe, Galley, Abdel-Fattah, & Webster, 2003; Qaddourah et al, 2014; Yilmaz, Yentur, & Saruhan-Direskeneli, 2005).…”