Preeclampsia In Chinese Han Population Research Articles

Impact of SLC23A1 and SLC23A2 Polymorphisms on the Risk for Preeclampsia in a Chinese Han Population.

Solute carrier family 23 member 1 (SVCT1) and solute carrier family 23 member 2 (SVCT2), encoded by SLC23A1 and SLC23A2, may be associated with preeclampsia (PE). The purpose of this study was to investigate the association between polymorphisms of SLC23A1 and SLC23A2 and PE in Chinese Han population. The primers and double-labeled probes were designed according to the SNPs of rs10063949 in SLC23A1, rs6133175 and rs1279683 in SLC23A2. Genomic DNA was extracted from peripheral blood of 2,066 subjects (1,029 with PE and 1,037 without PE), and Taqman real-time PCR was used to detect the three SNPs. We observed a significant difference in genotypic frequency of the SLC23A2 rs6133175 polymorphism (χ2=8.08, p=0.02) between PE patients and controls, while no significant differences were found in the allelic frequencies (χ2=1.45, p=0.23). Then we fractionized these samples into the dominant model of the allele G (GG/AG+AA group) or the recessive model of the A allele (AA/AG+GG group), and observed a significant difference under the recessive model of the A allele (p=0.01, OR=0.71, 95% CI 0.55-0.92). Furthermore, there were no significant differences in the genotypic and allelic frequencies of rs10063949 and rs1279683 between PE patients and controls (for rs10063949, χ2=2.96, p=0.23 by genotype, χ2=2.11, p=0.15 by allele; for rs1279683, χ2=1.52, p=0.47 by genotype, χ2=0.64, p=0.44 by allele). We first found that SLC23A2 rs6133175 may be the certain genetic polymorphisms modulating their effects in the development of PE in a Chinese Han population and the AG or GG genotypes may be a risk factor for PE.

C677T Gene Polymorphism of MTHFR Is a Risk Factor for Impaired Renal Function in Pregnant Women With Preeclampsia in the Chinese Han Population.

Impaired renal function in pregnant women with preeclampsia is particularly common, yet there is no consensus about implementation. This lack of consensus is due in part to uncertainty about risks for disease progression. Limited evidence suggests that C677T gene polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR C677T) may affect impaired renal function in pregnant women with preeclampsia in Chinese Han population. To investigate the association between MTHFR C677T and impaired renal function in pregnant women with preeclampsia, a total of 327 pregnant women diagnosed with gestational hypertension (GH) or preeclampsia-eclampsia (PE) from January 2016 to December 2021 were selected as the study subjects. The personal information, gestational information, clinical indicators, and the C677T gene polymorphism of MTHFR were tested. Compared with the GH group, the PE renal function impairment group had increased in blood pressure, homocysteine level, liver and kidney function indicators (creatinine, uric acid, urea nitrogen, cystatin C, alanine aminotransferase, aspartate aminotransferase, cholyglycine), and blood lipids (total cholesterol, triglycerides and low density lipoprotein) but had reductions in plasma protein (total protein, albumin, globulin, prealbumin), trace elements (calcium and zinc), prothrombin time and fibrinogen. The homocysteine level in the TT genotype was higher than that in the CC and CT genotypes. Binary logistic regression analysis showed that the MTHFR C677T gene polymorphism was associated with PE renal function impairment in the recessive model (OR: 1.620, 95% CI: 1.033–2.541, P < 0.05). These findings show that the C677T gene polymorphism of MTHFR is an independent risk factor for impaired renal function in pregnant Chinese Han women with PE.

Genetic susceptibility analysis of FGF5 polymorphism to preeclampsia in Chinese Han population.

Fibroblast growth factor 5 (FGF5), which is a well-established causative factor for blood pressure, has been identified as a susceptibility gene for preeclampsia (PE) in European and Central Asian women. Here, we examined whether polymorphism rs16998073 in FGF5 confer a significant risk to PE in Chinese Han population by case-control association analysis. FGF5 rs16998073 was genotyped by Sanger sequencing in women with preeclampsia (n = 187) and healthy controls (n = 229) of Han Chinese. We found the frequency of rs16998073T allele was significantly higher in PE patients than that in controls. Next, we utilized dual-luciferase reporter assays and electrophoretic mobility shift assay (EMSA) reactions to investigate whether rs16998073 different alleles could affect the transcriptional activity of FGF5. The dual luciferase reporter assay showed that T allele increased the transcriptional efficiency by 1.5-fold compared with the G allele. Similarly, EMSA revealed that the T allele had a strong transcription factor binding strength compared with the G allele. We then examined the mRNA and protein expression levels of FGF5 in placental tissues by real-time PCR and Western blot assays. We found FGF5 were significantly upregulated in placental tissues from PE patients or PE mouse model than their corresponding controls. In addition, in vitro cell experiments confirmed that FGF5 could promote cell apoptosis of HTR8/SVneo and inhibit cell invasion. Taken together, our data provide evidence implicating rs16998073 of FGF5 as a functional genetic risk variant for PE disease and FGF5 might participate in development of PE disease.

Association study of hypertension susceptibility genes ITGA9, MOV10, and CACNB2 with preeclampsia in Chinese Han population

Objective Preeclampsia (PE) is a disorder that occurs during the pregnancy and could affect the maternal and perinatal mortality as well as morbidity. The aim of our study is to investigate the associations between the hypertension susceptibility genes ITGA9, MOV10 and CACNB2 with PE in Chinese Han population. Methods A case–control study including 178 PE patients and 202 healthy controls was conducted to assess the associations between three loci (ITGA9 rs155524, MOV10 rs2932538 and CACNB2 rs4373814) and PE. The TaqMan probe assay was applied for genotyping in our study. Quantitative real-time PCR was performed to detect the mRNA expression levels of ITGA9, MOV10 and CACNB2. ELISA was carried out to detect the concentration of serum sFlt-1 or PLGF. Results Our study detected no significant differences in allelic frequencies of three SNPs between PE patients and healthy controls. In the genetic model, the results showed that the patients with ITGA9 rs155524 GA or AA genotypes had a higher risk of PE development compared to those with GG genotype in codominant model. And PE patients had a higher frequency of GA + AA genotypes based on the dominant model. Subgroup analysis showed ITGA9 rs155524 was associated with early-onset PE but not with late-onset PE. No association was observed between MOV10 and CACNB2 with PE in any genetic model and subgroup analysis. Quantitative real-time PCR results showed that ITGA9 mRNA expression level was apparently increased in the placental tissues of PE patients. In addition, ITGA9 expression levels of GA + AA subjects were apparently higher than that in the genotype GG of placental tissues. sFlt-1/PLGF ratio was higher in GA + AA subjects than that in GG subjects. Regression analysis revealed that ratio of sFlt-1/PLGF was positively correlated with ITGA9 mRNA expression level. Conclusion This study has identified ITGA9 is a promising candidate susceptibility gene for early-onset PE. Our findings demonstrated that the high expression of ITGA9 might be associated with an increased risk of PE.

HSPA1L rs1061581 polymorphism is associated with the risk of preeclampsia in Han Chinese women.

Preeclampsia (PE) is an excessive systemic inflammation response with dysfunction of endothelial. As a stress protein, heat shock protein 70 (HSP70) plays a pivotal role in protecting cells against apoptosis, oxidative damage and genetic damage. In humans, three genes encode members of the HSP70 class: HSPA1A, HSPA1B and HSPA1L. Our study was to investigate the association between genetic variations of HSPA1L and the susceptibility for PE in Chinese Han population. The polymorphisms of rs2227956, rs1043618 and rs1061581 in HSPA1L were genotyped by TaqMan allelic discrimination real time polymerase chain reaction (PCR) in 929 PE patients and 1024 healthy pregnant women. Statistic difference of the genotypic and allelic frequencies were found in HSPA1L rs1061581 between PE patients and controls (χ2 = 29.863, P < 0.001 by genotype; χ2 = 27.298, P < 0.001, OR = 1.874, 95%CI 1.476–2.379 by allele) and HSPA1L rs1061581 A alleles occurred more frequently in PE patients compared with healthy controls (PE vs. controls 10.28% vs. 5.76%). Furthermore, we divided the PE cases into early-onset/late-onset PE and mild/severe PE subgroups and found statistical differences in genotypic and allelic frequencies of the HSPA1L rs1061581 between early-onset PE, late-onset PE, mild PE, severe PE and controls, respectively. Moreover, HSPA1L rs1061581 A alleles were more frequent in early-onset PE, late-onset PE, mild PE and severe PE than controls respectively. Therefore, we concluded that HSPA1L rs1061581 polymorphism is associated with the risk of PE in Han Chinese women and A alleles may play a role in the susceptibility for PE.

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

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 χ 2 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 (χ 2 = 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 (χ 2 = 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. (χ 2 = 8.53 p = .01, χ 2 = 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, χ 2 = 0.17, p = .92; for allelic frequency, χ 2 = 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.

Polymorphism-801G/A in the 3′-untranslated region of CXCL12 is not associated with preeclampsia in Chinese Han population

ABSTRACTObjective: We investigated whether the CXCL12-801G/A polymorphism was associated with preeclampsia (PE) susceptibility in a Chinese Han population. Methods: We examined 912 PE women and 1025 controls for the CXCL12-801G/A polymorphism by polymerase chain reaction (PCR) and correlations with clinical characteristics were examined. Results: No significant differences in genotypic and allelic frequencies of CXCL12-G801A were found between cases and controls (genotype: χ2 = 2.095, p = 0.351; allele: χ2 = 1.713, p = 0.191). There were also no significant differences between early/late-onset or mild/severe PE and control groups. Conclusion: The results indicate that 801G/A in CXCL12 may not play a major role in pathogenesis of PE in a Chinese Han population.

Polymorphisms of the IL27 gene in a Chinese Han population complicated with pre-eclampsia.

IL-27 could inhibit the development of Th17 cells, and the Th17/regulatory T-cell imbalance may reverse maternal tolerance in pre-eclampsia (PE). The aim of this study was to investigate the association between genetic polymorphisms in IL27 with PE. Three SNPs in IL27 (rs153109, rs17855750, and rs181206) were genotyped in a Chinese Han cohort of 1040 PE patients and 1247 normal pregnant women using the TaqMan allelic discrimination real-time PCR method. The CC genotypic distribution of rs153109 was significantly higher among cases than controls (19.1% versus 13.3%, odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.23–1.93, p < 0.001), and the CT genotype was found to be significantly lower in cases than controls (41.7% versus 49.0%, OR: 0.74, 95% CI: 0.63–0.88, p < 0.001), disputing existing reports indicating the allele frequency of rs153109 is not significantly different between PE patients and controls. Additionally, the CC genotype of rs153109 was significantly more prevalent in PE cases than controls using a recessive model (p < 0.001). The allelic and genotypic frequencies of rs17855750 and rs181206 were not significantly different between two groups. Our results reveal that IL27 polymorphisms may be involved in the development of PE in Chinese Han population.

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Objectives The development of preeclampsia is considered to be related to maternal immune and genetic factors. HLA-C is one of the major histocompatibility antigens that plays an important role in regulating maternal fetal interface. However, epidemiological studies show that paternal risk factors can play a role in the development of preeclampsia. The aim of this study is to explore the relationship between paternal and fetal HLA-C allelic polymorphisms and preeclampsia in Chinese Han population. Methods 34 spouses and fetuses of women with preeclampsia and 37 spouses and fetuses of healthy pregnant women were included in the case-control study. All pregnant women were at the third trimester of gestation. The HLA-C genes from blood genomic DNA were genotyped by polymerase chain reaction–sequencing-based typing (PCR-SBT) genotyping method. The associations of HLA-C alleles with the disease were expressed as P and odds ratios (ORs). Results No differences were observed in the spouses’ age, body mass index, contraception method or previous history of hypertension and cardiovascular disease. Gestational age was shorter (36.39 ± 3.15 vs. 39.31 ± 1.14, p p ∗ 08:01:01G was significantly higher in the spouses of preeclamptic women, compared with that in the spouses of normotensive women (14.7 vs. 2.7%, P = 0.010, OR = 6.207, 95%CI (1.308, 29.451)). There was no statistical difference in the frequency of fetal HLA-C alleles ( p > 0.05). Conclusions Pregnant women with spouses carrying HLA-C ∗ 08:01:01G have a greater risk for the developing of preeclampsia in Chinese Han population. Disclosures H. Yu: None. N. Pan: None. Y. Shen: None. S. Jin: None. J. Zhai: None. D. Qiao: None. L. Chen: None. W. Xu: None. F. Miao: None. Y. He: None. M. Ren: None. J. Zhang: None.

Interleukin-1β-31C/T and -511T/C polymorphisms were associated with preeclampsia in Chinese Han population.

ObjectiveThe purpose of our study is to investigate the relationship between IL-1β -31C/T (rs1143627) and -511T/C (rs16944) polymorphisms and the preeclampsia (PE), and analyze the Linkage disequilibrium (LD) and haplotype frequency of the two polymorphism loci.MethodsPolymorphisms at -31C/T and -511T/C of IL-1β were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP) in 232 PE and 447 control subjects. Genotype and allele frequencies between case-control groups were compared by chi-square(X2) tests. Two-point LD and haplotype frequency analyses were done with the software Haploview4.2.ResultsSignificant statistical differences were found between PE and control groups regarding genotype and allele frequencies of the two polymorphisms of IL-1β (For IL-1β -31C/T: X2 = 11.478, P = 0.003; For IL-1β-511T/C: X2 = 9.687, P = 0.008). LD analysis revealed that the IL-1β -31C/T SNP was in high LD with the IL-1β-511C/T SNP(D′ = 0.92, r2 = 0.79). Both CT and TC haplotypes showed significant differences between case and control groups. Only the plasma level of Prothrombin Time had a significantly statistical difference among TT, CT and CC groups of the preeclamptic two polymorphisms of IL-1β-31C/T and -511T/C (for IL-1β-31C/T, F = 1.644, P = 0.01; F = 1.587, P = 0.016).ConclusionOur results revealed IL-1β was associated with the PE in Chinese Han population. The CT haplotype may increase the risk of PE, while haplotype TC could be considered as a protective haplotype of PE.

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.