Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia

Unbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs1785575...

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Main Authors: Aiping Chen, Huifang Zhao, Jingli Wang, Ru Zhang, Jingjing Liu, Xin Zhao, Congying Li, Xuewen Jia, Xueying Li, Yan Lin, Mingzhen Guo, Sai Li, Chao Liu, Yuan Li, Shiguo Liu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/4683798
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author Aiping Chen
Huifang Zhao
Jingli Wang
Ru Zhang
Jingjing Liu
Xin Zhao
Congying Li
Xuewen Jia
Xueying Li
Yan Lin
Mingzhen Guo
Sai Li
Chao Liu
Yuan Li
Shiguo Liu
author_facet Aiping Chen
Huifang Zhao
Jingli Wang
Ru Zhang
Jingjing Liu
Xin Zhao
Congying Li
Xuewen Jia
Xueying Li
Yan Lin
Mingzhen Guo
Sai Li
Chao Liu
Yuan Li
Shiguo Liu
author_sort Aiping Chen
collection DOAJ
description Unbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs17855750, rs2027432, rs2275913, rs763780, rs4819554, and rs13015714) and oxidative stress (rs1695, rs4680, rs1800566, rs4807542, rs713041, rs7579, rs230813, rs1004467, rs3824755, and rs9932581) to investigate whether these polymorphisms were associated with susceptibility to PE in a Chinese Han population. In this present study, we collected these data of experimental and clinical from above studies for haplotype analysis of inflammation-related SNPs in 631 PE patients and 720 normal pregnancy and oxidative stress-related SNPs in 342 PE patients and 457 normal pregnancies for susceptibility to PE. The data of genotype distribution and allele frequency comparisons after correction for multiple comparisons (P/8 or P/10) showed 2 among the 8 candidate inflammation-related SNPs have significant differences (rs2027432 genotype χ2=407.377,p<0.001,p<0.00625). Moreover, the minor alleles of rs2027432 T (minor allele χ2=450.923,p<0.001,p<0.00625;OR=21.439,95%CI=15.181‐30.278) and rs4819554 G (minor allele χ2=163.465,p<0.001,p<0.00625;OR=5.814,95%CI=4.380‐7.719) were confirmed as risk allele of PE, respectively. Our analysis revealed rs2027432 (TT) of NLRP3 and rs4819554 (GG) of IL-17RA are risk factors for PE. However, no significant difference was found at the oxidative stress-related SNPs. In the candidate loci for oxidative stress, we also identified 3 SNP matches (rs4807542 and rs713041, rs230813 and rs75799, rs1004467 and rs3824755) that had high linkage disequilibrium (LD) with each other and were selected as a block (r2=0.98,r2=0.97,r2=0.97,r2>0.9), and the GT and GC haplotypes of rs4807542 and rs713041 in GPX4 showed significant differences between the PE and control groups (χ2=5.143,p=0.0233,p<0.05;χ2=6.373,p=0.0116,p<0.05). So, we inferred that polymorphisms of NLRP3 rs2027432 and IL-17RA rs4819554, which are related to inflammation, and the rs713041 variant of GPX4, which is related to oxidative stress, were associated with susceptibility to PE. The GT and GC haplotypes of rs4807542 and rs713041 in GPX4 may increase the risk of PE in the Chinese Han population.
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spelling doaj-art-13c93334ce0c4a1c898399f5482bc4132025-02-03T01:30:30ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/46837984683798Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to PreeclampsiaAiping Chen0Huifang Zhao1Jingli Wang2Ru Zhang3Jingjing Liu4Xin Zhao5Congying Li6Xuewen Jia7Xueying Li8Yan Lin9Mingzhen Guo10Sai Li11Chao Liu12Yuan Li13Shiguo Liu14Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaSchool of Nursing, Weifang University of Science and Technology, Shouguang, ChinaMedical Genetic Department, Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, ChinaMedical Genetic Department, Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Laboratory, Qingdao Municipal Hospital, Qingdao, ChinaDepartment of Gynecology and Obstetrics, Qingdao Women and Children’s Hospital of Qingdao University, Qingdao, ChinaGynecology, Heze Municipal Hospital, ChinaDepartment of Emergency, Shengli Oilfield Central Hospital, ChinaSchool of Nursing, Binzhou Polytechnic, Binzhou, ChinaClinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, ChinaMedical Laboratory, Qingdao Women and Children’s Hospital of Qingdao University, Qingdao, ChinaBiology Teaching and Research Department, Fourth Middle School of Qingdao Economic and Technological Development Zone, Qingdao, ChinaDepartment of Basic Medicine, College of Pharmacy, Jining Medical University, Rizhao, ChinaDepartment of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaMedical Genetic Department, Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, ChinaUnbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs17855750, rs2027432, rs2275913, rs763780, rs4819554, and rs13015714) and oxidative stress (rs1695, rs4680, rs1800566, rs4807542, rs713041, rs7579, rs230813, rs1004467, rs3824755, and rs9932581) to investigate whether these polymorphisms were associated with susceptibility to PE in a Chinese Han population. In this present study, we collected these data of experimental and clinical from above studies for haplotype analysis of inflammation-related SNPs in 631 PE patients and 720 normal pregnancy and oxidative stress-related SNPs in 342 PE patients and 457 normal pregnancies for susceptibility to PE. The data of genotype distribution and allele frequency comparisons after correction for multiple comparisons (P/8 or P/10) showed 2 among the 8 candidate inflammation-related SNPs have significant differences (rs2027432 genotype χ2=407.377,p<0.001,p<0.00625). Moreover, the minor alleles of rs2027432 T (minor allele χ2=450.923,p<0.001,p<0.00625;OR=21.439,95%CI=15.181‐30.278) and rs4819554 G (minor allele χ2=163.465,p<0.001,p<0.00625;OR=5.814,95%CI=4.380‐7.719) were confirmed as risk allele of PE, respectively. Our analysis revealed rs2027432 (TT) of NLRP3 and rs4819554 (GG) of IL-17RA are risk factors for PE. However, no significant difference was found at the oxidative stress-related SNPs. In the candidate loci for oxidative stress, we also identified 3 SNP matches (rs4807542 and rs713041, rs230813 and rs75799, rs1004467 and rs3824755) that had high linkage disequilibrium (LD) with each other and were selected as a block (r2=0.98,r2=0.97,r2=0.97,r2>0.9), and the GT and GC haplotypes of rs4807542 and rs713041 in GPX4 showed significant differences between the PE and control groups (χ2=5.143,p=0.0233,p<0.05;χ2=6.373,p=0.0116,p<0.05). So, we inferred that polymorphisms of NLRP3 rs2027432 and IL-17RA rs4819554, which are related to inflammation, and the rs713041 variant of GPX4, which is related to oxidative stress, were associated with susceptibility to PE. The GT and GC haplotypes of rs4807542 and rs713041 in GPX4 may increase the risk of PE in the Chinese Han population.http://dx.doi.org/10.1155/2020/4683798
spellingShingle Aiping Chen
Huifang Zhao
Jingli Wang
Ru Zhang
Jingjing Liu
Xin Zhao
Congying Li
Xuewen Jia
Xueying Li
Yan Lin
Mingzhen Guo
Sai Li
Chao Liu
Yuan Li
Shiguo Liu
Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia
Journal of Immunology Research
title Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia
title_full Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia
title_fullStr Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia
title_full_unstemmed Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia
title_short Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia
title_sort haplotype analysis of candidate genes involved in inflammation and oxidative stress and the susceptibility to preeclampsia
url http://dx.doi.org/10.1155/2020/4683798
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