Haplotype Analysis of Candidate Genes Involved in Inflammation and Oxidative Stress and the Susceptibility to Preeclampsia
| Autor: | Aiping Chen, Xin Zhao, Congying Li, Xueying Li, Chao Liu, Ru Zhang, Xuewen Jia, Mingzhen Guo, Yan Lin, Huifang Zhao, Jingli Wang, Shiguo Liu, Sai Li, Yuan Li, Jingjing Liu |
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| Rok vydání: | 2020 |
| Předmět: |
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China Candidate gene Genotype Article Subject Immunology Single-nucleotide polymorphism Biology medicine.disease_cause Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Gene Frequency Pre-Eclampsia Pregnancy Polymorphism (computer science) NLR Family Pyrin Domain-Containing 3 Protein medicine Humans Immunology and Allergy Genetic Predisposition to Disease Allele frequency Genetic Association Studies Inflammation Receptors Interleukin-17 030219 obstetrics & reproductive medicine Haplotype General Medicine RC581-607 Phospholipid Hydroperoxide Glutathione Peroxidase Oxidative Stress Haplotypes 030220 oncology & carcinogenesis Female Immunologic diseases. Allergy Oxidative stress Research Article rs4680 |
| Zdroj: | Journal of Immunology Research Journal of Immunology Research, Vol 2020 (2020) |
| ISSN: | 2314-7156 2314-8861 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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