Jingli Wang

Genetic variations in IL1A and IL1RN are associated with the risk of preeclampsia in Chinese Han population

Preeclampsia (PE) is an excessive systemic inflammation response with dysfunction of endothelial. Our study was to investigate the association between genetic variations in IL-1 and the susceptibility to PE in Chinese Han population. 402 PE patients and 554 normal pregnant women of third trimester were enrolled. The polymorphisms of rs315952 in IL1RN and rs17561 in IL1A were genotyped by TaqMan allelic discrimination real-time PCR. Obviously statistic difference of the genotypic frequencies were found in both of IL1RN rs315952 and IL1A rs17561 between cases and controls (for rs315952, P = 0.001; for rs17561, P = 0.021.). For rs315952, the C allele was associated with development of PE (P = 0.003, OR = 1.319, 95%CI 1.099–1.583). Patients with CC or CT genotype were less likely to develop severe PE than patients carrying TT genotype(P < 0.001, OR = 0.24, 95%CI 0.15–0.40). For rs17561, the C allele was the risk factor for predisposition to PE (P = 0.012, OR = 1.496, 95%CI 1.089–2.055). Our results suggest IL1RN and IL1A may involve in the development of PE in Chinese Han population.

Genetic variations in the vitamin-D receptor (VDR) gene in preeclampsia patients in the Chinese Han population

Previous studies have indicated that vitamin D deficiency is linked to a risk of preeclampsia (PE). The aim of our study was to investigate the association between genetic variations in the vitamin-D receptor (VDR) gene and the susceptibility to PE in the Chinese Han population. We examined the genotypes VDR rs2228570, rs11568820 and rs1544410 in 402 PE patients and 554 normal pregnant women in the third trimester by TaqMan allelic discrimination real-time polymerase chain reaction. The clinical data of the individuals were collected to enable genotype–phenotype analysis. A significant statistical difference in the genotypic frequencies of rs2228570 between cases and controls was found (χ2=13.750, P=0.001). The G allele was the risk factor for the risk of PE (χ2=9.456, P=0.002, OR=1.137, 95% CI 1.111–1.610). There was no difference in the genotypic and allelic distributions of rs11568820 and rs1544410 between the two groups (P&gt; 0.05). Our results provide evidence for a possible link between VDR and the development of PE in the Chinese Han population.

Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia

Background/Aims: Accumulating evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with exaggerated activation of the innate immune system plays a critical role in the development of preeclampsia (PE). In this study, we investigated whether polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with susceptibility to PE in the Chinese Han population. Methods: We recruited 987 PE patients and 1227 healthy pregnant women. Two polymorphisms (rs3775291 and rs3775296) located in TLR3 were genotyped by TaqMan allelic discrimination real-time PCR. The association between the genotype or allele frequencies and PE was examined using chi-square tests. Clinical data were compared between cases and controls using Students t test. Results: No significant difference was determined in the genetic distribution of rs3775291 and rs3775296 between cases and controls. There were also no significant differences in the genotype and allele frequencies of either SNP between healthy pregnant women and patients with late or early onset PE, or with mild or severe PE. Conclusion: Although this is the first study of the association between TLR3 polymorphisms and preeclampsia, we found that TLR3 polymorphisms are unlikely to play a significant role in the development of preeclampsia in the Chinese Han population.

Role of IL-17 Variants in Preeclampsia in Chinese Han Women.

Previous studies have suggested an important role for IL-17, mainly secreted by Th17 cells, in the development of systemic inflammation in preeclampsia (PE). This study therefore investigated the association between genetic variants in IL-17A, IL-17F, and IL-17RA and susceptibility to PE in Chinese Han women. We recruited 1,031 PE patients and 1,298 controls of later pregnant women, and used TaqMan allelic discrimination real-time PCR to genotype the polymorphisms of IL17A rs2275913, IL-17F rs763780, and IL-17RA rs4819554. No significant differences in genotypic or allelic frequencies were found at all three polymorphic sites between PE patients and controls (rs2275913: genotype χ2 = 0.218, p = 0.897 and allele χ2 = 0.157, p = 0.692, OR = 1.024, 95%CI 0.911–1.152; rs763780: genotype χ2 = 1.948, p = 0.377 and allele χ2 = 1.242, p = 0.265, OR = 0.897, 95%CI 0.741–1.086; rs4819554: genotype χ2 = 0.633, p = 0.729 and allele χ2 = 0.115, p = 0.735, OR = 1.020, 95%CI 0.908–1.146). There were also no significant differences in genetic distributions between mild/severe PE or early/late-onset PE and control subgroups. Our data indicate that the genetic variants of rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA may not play a role in the pathogenesis of PE in Chinese Han women. However, these findings should be confirmed in other ethnic populations.

Association between COMT Val158Met polymorphism and preeclampsia in the Chinese Han population.

ABSTRACT Objective: Previous studies have been indicated that catechol-O-methyltransferase gene (COMT) might play a significant role in the development of preeclampsia (PE). Our study aims to investigate the association between polymorphism in COMT with the susceptibility to PE in Chinese Han women. Method: A total of 1028 PE patients and 1399 normal pregnant women were enrolled. We detected the genotyping of COMT Val158Met loci by the TaqMan allelic discrimination real-time PCR . Results: No significant difference in the genotypic and allelic distribution was found between the two groups (genotype: X2 = 0.583, p = 0.747; allele:X2 = 0.526, p = 0.468). Conclusion: The COMT Val158Met polymorphism might not be associated with PE in Chinese women.

The NLRP3 rs10754558 polymorphism is a risk factor for preeclampsia in a Chinese Han population

Abstract Objective: Previous studies have indicated that the nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) inflammasome is activated by monosodium urate in the trophoblast of preeclampsia (PE) patients, leading to augmented placental IL-1β levels. Thus, the purpose of our study was to investigate the association between NLRP3 polymorphisms, rs10754558 and rs2027432, and PE in Chinese Han population. Methods: The NLRP3 polymorphisms, rs10754558 and rs2027432, were genotyped by real-time PCR in 1024 PE patients and 1194 control subjects. A χ2 test was used to compare the genetic distribution between the two groups, and an analysis of variance was used to conduct the genotype–phenotype analysis. Results: We demonstrated a significant difference in genotypic frequency of the rs10754558 (χ2 = 9.97, p = .007) in NLRP3 between PE patients and controls. Additionally, there was a significant difference between cases and controls in the dominant model of G allele (χ2 = 7.70, p = .006, odds ratio =0.77, 95%confidence interval 0.64–0.93). What’s more, the genotypes distributions of rs10754558 were found to be associated with both the severe and late onset PE. (χ2 = 8.53 p = .01, χ2 = 9.24, p = .01.) However, no significant statistic differences were found in the genotypic distributions and allelic frequencies for rs2027432 between two groups (for genotypic distribution, χ2 = 0.17, p = .92; for allelic frequency, χ2 = 2.26, p = .13, odds ratio =0.90, 95% confidence interval 0.79–1.03). Conclusions: Our results reveal that NLRP3 may be involved in the development of PE in a Chinese Han population. However, further validation of the associations of other NLRP3 SNPs with PE in other populations is required.

Impact of IL-22 and IL-22 receptor alpha 1 polymorphisms on preeclampsia risk in Chinese Han women

Previous studies have indicated that an increased inflammatory response plays an important role in preeclampsia (PE), and rising levels of interleukin (IL)‐22 can trigger inflammation and hyperproliferation, leading to increased production of several pro‐inflammatory cytokines such as IL‐1, IL‐6, and IL‐8. We aimed to investigate the association between polymorphisms of IL‐22 and IL‐22 receptor alpha 1 gene (IL‐22RA1) and PE in Chinese Han population. Single nucleotide polymorphisms (SNPs) rs2227485 in IL‐22 and rs3795299 in IL‐22RA were genotyped by Taqman real‐time PCR in 1071 PE patients and 1263 control subjects. Differences in genetic distribution were compared between two groups using the chi‐square test. Significant differences were observed in genotypic and allelic frequencies of IL‐22RA1 rs3795299 between healthy controls and PE patients (P < 0.001 by genotype; P = 0.001, odds ratio = 1.253, 95% confidence interval 1.103‐1.424 by allele). There were also significant differences in genotypic and allelic frequencies of rs3795299 between late‐onset/mild PE and control groups. In addition, we found obvious statistic difference for the allele of early‐onset PE/the genotype of late‐onset PE and control subgroups for IL‐22 rs2227485. IL‐22 rs2227485 and IL‐22RA1 rs3795299 may be associated with the development of PE in Chinese Han population. However, further validation is required in other populations, as well as an evaluation of the association of other SNPs in IL‐22 and IL‐22RA1 with PE.

Evaluation of Glutathione Peroxidase 4 role in Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific syndrome that may be lifethreatening to pregnancies and fetus. Glutathione Peroxidase 4 (GPx4) is a powerful antioxidant enzyme that can provide protection from oxidative stress damage which plays a pivotal role in the pathology of PE. Therefore, this study aims to investigate the association between Gpx4 polymorphisms and the susceptibility to PE in Chinese Han women. TaqMan allelic discrimination real-time PCR was used to perform the genotyping of rs713041 and rs4807542 in 1008 PE patients and 1386 normotensive pregnancies. Obviously statistical difference of genotypic and allelic frequencies were found of rs713041 in GPx4 between PE patients and controls and the C allele has the higher risk for pathogenesis of PE (χ2 = 12.292, P = 0.002 by genotype; χ2 = 11.035, P = 0.001, OR = 1.216, 95% CI 1.084–1.365 by allele). Additionally, when subdividing these samples into CC + CT and TT groups, we found a significant difference between the two groups (χ2 = 11.241, P = 0.001, OR = 1.417, 95% CI 1.155–1.738). Furthermore, the genotype of rs713041 was found to be associated with the mild, severe and early-onset PE. Our results suggest that rs713041 in GPx4 may play a key role in the pathogenesis of PE.

Effects of Klotho polymorphisms on Preeclampsia risk in a case-control study

Preeclampsia (PE) is a serious disorder of human pregnancy and always is accompanied with multi-organ disorder, which severely threatens the health of both the mothers and the offspring. The oxidative stress and genetic factors involves in the development of PE. The Klotho encodes Klotho protein that is capable of increasing resistance to oxidative stress. Thus, we designed this case-control study to investigate the association between Klotho polymorphisms and the susceptibility to PE in Chinese Han women. Two single nucleotide polymorphisms (SNPs) (rs1207568 and rs564481) in Klotho were selected to be genotyped in 1002 PE patients and 1384 normal controls with TaqMan allelic discrimination real-time PCR technology. There were no significant differences in genotypic or allelic frequencies at both polymorphic sites between PE patients and controls (rs1207568: χ2 = 2.386, p = 0.303 by genotype, χ2 = 2.357, p = 0.125, OR = 1.127, 95%CI 0.968-1.312 by allele; rs564481: χ2 = 1.195, p = 0.550 by genotype, χ2 = 0.018, p = 0.894, OR = 1.010, 95%CI 0.875-1.165 by allele). Furthermore, we divided the cases into mild vs severe and early-onset vs late-onset subgroups and then analyzed the relationships between these subgroups and the control group respectively. As a consequence, no significant differences were found for both SNPs in each case. These results suggested that the genetic variants of rs1207568 and rs564481 in Klotho may not play a pivotal role in the pathogenesis of PE in Chinese Han women.

Identification of SEPP1 polymorphisms is not a genetic risk factor for preeclampsia in Chinese Han women: A clinical trial and experimental study

Background: SEPP1 encodes selenoprotein P, which involved in oxidative stress and plays an important role in the development of preeclampsia (PE). The aim of this study was to investigate the association between PE and genetic variants of SEPP1 in Chinese Han women. Methods: In all, 2434 unrelated pregnant women were recruited, including 1034 PE cases and 1400 normal pregnant controls. TaqMan allelic discrimination real-time PCR method was used to genotype the 2 polymorphisms of rs7579 and rs230813 in SEPP1. Results: No statistically significant difference in genotypic or allelic frequencies were found at the 2 genetic variants in SEPP1 between PE patients and controls (rs7579: genotype &khgr;2 = 2.417, P = .299 and allele &khgr;2 = 0.197, P = .761, odds ratio 1.049, 95% confidence interval 0.744–1.151; rs230813: genotype &khgr;2 = 3.273, P = .195 and allele &khgr;2 = 0.252, P = .615, odds ratio 0.971, 95% confidence interval 0.864–1.091). There were also no statistically significant differences in genetic distributions between mild/severe PE or early/late-onset PE and control subgroups. Conclusion: Our data indicate that the 2 genetic variants of rs7579 and rs230813 in SEPP1 may not play a role in the pathogenesis of PE in Chinese Han Women.