Abstract
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.
Highlights
Preeclampsia (PE) is a serious complication of pregnancy characterized by hypertension and proteinuria after 20 weeks of gestation [1]
Because genetic factors are involved in the development of PE, in this study, we examined single-nucleotide polymorphisms (SNPs) and haplotypes in inflammation- and oxidative stress-associated candidate genes for susceptibility to PE in a Chinese Han population based on our previous study
The PE group had higher neutrophil counts than the control group (p = 0:015); no significant difference was found in the neutrophil counts for the oxidative stress group (p = 0:130)
Summary
Preeclampsia (PE) is a serious complication of pregnancy characterized by hypertension and proteinuria after 20 weeks of gestation [1]. The clinical symptoms of PE are reflected in three aspects; the first involves placental perfusion dysfunction followed by a systemic inflammatory response, the second is vascular endothelial damage, and the last is oxidative stress [1]. These placental factors are released into the maternal body and cause the clinical symptoms of PE [6]. T lymphocytes are inclined toward Th1 cells and produce an increase in Th1 cytokines and a decrease in Th2 cytokines in PE [9, 12] This unbalanced immunotolerance causes inflammatory cells to be overactive, adheres to the vascular endothelium, and releases inflammatory factors, such as IL family members and the inflammasome, which eventually abnormally remodels the vascular endothelium to cause PE. Because genetic factors are involved in the development of PE, in this study, we examined single-nucleotide polymorphisms (SNPs) and haplotypes in inflammation- and oxidative stress-associated candidate genes (inflammation genes IL-22, IL-27, NLRP3, IL-17, and IL-1; oxidative stress genes GSTP1, GPX, COMT, NQO1, SEEP1, CYP17, and CYBA) for susceptibility to PE in a Chinese Han population based on our previous study
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
