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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).

SUBMITTER: Harmon QE

PROVIDER: S-EPMC4040534 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Polymorphisms in inflammatory genes are associated with term small for gestational age and preeclampsia.

Harmon Quaker E QE Engel Stephanie M SM Wu Michael C MC Moran Thomas M TM Luo Jingchun J Stuebe Alison M AM Avery Christy L CL Olshan Andrew F AF

American journal of reproductive immunology (New York, N.Y. : 1989) 20140404 5

<h4>Problem</h4>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.<h4>Method of study</h4>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.<h4>Results ...[more]

PMID: 24702779

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Project description:To investigate the potential risk factors for small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) late-term infants, 100 cases of single full-term SGA infants delivered in the Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University in 2017 were enrolled as the SGA group. A total of 100 healthy AGA who were born at the same time with the same gestational age were randomly included as the control group. The perinatal and postpartum adverse conditions of the two groups were recorded, and Apgar tests were performed on all newborns at 1 min (T1), 5 min (T2) and 10 min (T3) after birth. A follow-up survey was conducted in all patients at 6 and 12 months of age. At the second follow-up, the development quotient of the children was measured using the Gesell Developmental Schedule, and the perinatal risk factors of SGA were analyzed. The incidence of intrauterine distress, respiratory distress syndrome and infectious disease in the SGA group was significantly higher compared with that in the AGA group (P<0.05). The Apgar scores at T1, T2 and T3 were significantly lower in the SGA group compared with the AGA group (P<0.05). The Apgar score at T1 was lower compared with that at T2 in the SGA group (P<0.05), and the Apgar score at T2 was lower compared with that at T3 (P<0.05). The length of hospital stay in the SGA group was significantly longer compared with that in the AGA group (P<0.05). The development quotient at the 6 and 12th month in the SGA group was significantly lower compared with that in the AGA group (P<0.05). Logistic regression analysis showed that there was no correlation between SGA and maternal age, regardless of firstborn status, neonatal sex, mode of delivery and living environment. SGA was significantly associated with umbilical cord abnormalities, maternal pregnancy-induced hypertension, gestational diabetes, pregnancy infection and intrauterine distress (P<0.05). An abnormal umbilical cord, maternal pregnancy-induced hypertension, gestational diabetes, infection during pregnancy and intrauterine distress are all perinatal risk factors for SGA. Effective interventions are needed in clinical assessment to prevent the occurrence of SGA.

Project description:The goal of the study was to determine the early diagnostical potential of cardiovascular disease-associated microRNAs for prediction of small-for-gestational-age (SGA) and fetal growth restriction (FGR) without preeclampsia (PE). The whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case-control retrospective study, nested in a cohort, involved all pregnancies diagnosed with SGA (n = 37) or FGR (n = 82) without PE and 80 appropriate-for-gestational age (AGA) pregnancies selected with regard to equality of sample storage time. Gene expression of 29 cardiovascular disease-associated microRNAs was assessed using real-time RT-PCR. Upregulation of miR-16-5p, miR-20a-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, and miR-195-5p was observed in SGA or FGR pregnancies at 10.0% false positive rate (FPR). Upregulation of miR-1-3p, miR-20b-5p, miR-126-3p, miR-130b-3p, and miR-499a-5p was observed in SGA pregnancies only at 10.0% FPR. Upregulation of miR-145-5p, miR-342-3p, and miR-574-3p was detected in FGR pregnancies at 10.0% FPR. The combination of four microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) was able to identify 75.68% SGA pregnancies at 10.0% FPR in early stages of gestation. The detection rate of SGA pregnancies without PE increased 4.67-fold (75.68% vs. 16.22%) when compared with the routine first-trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation. The combination of seven microRNA biomarkers (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) was able to identify 42.68% FGR pregnancies at 10.0% FPR in early stages of gestation. The detection rate of FGR pregnancies without PE increased 1.52-fold (42.68% vs. 28.05%) when compared with the routine first-trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation. Cardiovascular disease-associated microRNAs represent promising early biomarkers with very suitable predictive potential for SGA or FGR without PE to be implemented into the routine screening programs.

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Polymorphisms in inflammatory genes are associated with term small for gestational age and preeclampsia.

Publications

Polymorphisms in inflammatory genes are associated with term small for gestational age and preeclampsia.

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