Polymorphisms In Preeclampsia Research Articles

Interleukin-6 (-174G/C), Interleukin-1β (-511 C/T), and Apolipoprotein B-100 (2488 C/T) Gene Polymorphism in Pre-Eclampsia.

Background and objectives: Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1β, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods: This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1β, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy-Weinberg equation and chi-square test to evaluate the results. Results: There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1β-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy-Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions: The polymorphisms of the IL-6, IL-1β, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy-Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied.

IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.

We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.

Association of MTHFR gene polymorphism in preeclampsia and recurrent pregnancy loss: A case-control study from South India

BackgroundPreeclampsia (PE) and recurrent pregnancy loss (RPL), both of which affect maternal and reproductive health, are obstetrical-gynecological issues. Pregnancies that meet one or more of these criteria are considered high risk. This study aims to examine and understand how specific methylation within the MTHFR gene (rs 1,801,131 and rs 1,801,133) polymorphisms may contribute to preeclampsia and recurrent miscarriages in the South Indian population. MethodsA combination of recurrent pregnancy loss and preeclampsia were taken as a case (146), and healthy controls (152) were enrolled in the study. 5 ml of human blood was taken after getting consent from the participants. The DNA was isolated from the peripheral blood lymphocytes and genotyped using ARMS-PCR. ResultThe findings of this study suggest that the MTHFR gene (rs1801131) is not associated with PE and RPL risk. A significant association has been observed between rs1801133 and the derived allele T (OR = 0.6, 95% CI -0.4-0.8, p = 0.001). Furthermore, a p-value of 0.01 was calculated for the homozygous recessive genotype TT (OR = 0.5, 95% CI - 0.29-0.1). ConclusionsThe results of this study suggest that preeclampsia and recurrent pregnancies are more common among South Indian women who carry a variant of the MTHFR gene 1,801,133. According to the conclusion, higher sample sizes and a wider study are necessary to verify these findings. More diverse and valuable information can be obtained through large sample sizes and combined studies, allowing the results to be applied to a wide population.

Effects of genetic polymorphisms of CYP2J2, CYP2C9, CYP2C19, CYP4F2, CYP4F3 and CYP4A11 enzymes in preeclampsia and gestational hypertension

IntroductionThe aim of this study was to investigate the effects of cytochrome P450 (CYP) 2J2, CYP2C9, CYP2C19 and CYP4F2, CYP4F3 and CYP4A11 genetic polymorphisms in preeclampsia and gestational hypertension (GHT) patients in a sample of Turkish population. Materials-methodsPatients (n = 168; 110 GHT and 58 preeclampsia) and healthy pregnant women (n = 155, controls) participated in the study. For genotyping, polymerase chain reaction (PCR) and restriction analysis (RFLP) were used. Substance levels were measured using LC-MS. ResultsPlasma DHET levels in GHT and preeclampsia patients were significantly lower than those in the control group (62.7%, 66.3% vs.100.0%, respectively, p < 0.0001). An increase in CYP2J2*7 allele frequency was observed in the preeclampsia group, as compared to GHT group (12.1% vs. 4.5%; odds ratio, O.R. = 2.88, p < 0.01). The frequencies of CYP2C19*2 and*17 alleles were higher in GHT group as compared to the control group (17.7% vs. 11.6%, O.R. = 1.99, p < 0.01; and 28.6% vs.18.4%, O.R. = 2.03, p < 0.01, respectively). An increased frequency of CYP4F3 rs3794987 G allele was found in GHT group as compared to the control group (48.0% vs. 38.0%; O.R. = 1.53, p < 0.01). DiscussionDHET plasma levels were significantly reduced in hypertensive pregnant groups as compared to the control group. The allele frequency distributions for CYP2J2*7, CYP2C19 *2, *17 and CYP4F3 rs3794987 were significantly different in hypertensive pregnant patients as compared to the healthy control subjects. Our results may suggest that investigated genetic polymorphisms may be useful in diagnosis and clinical management of GHT and preeclampsia patients.

Association of TNFSF11 rs2200287 and TNFSF11 rs2148072 gene polymorphisms in preeclampsia.

Various cytokines released by white blood cells like lymphocytes are linked to the immune system during pregnancy. The polymorphism of the TNFSF11 (rs2200287 and rs2148072) gene is related to the preeclampsia of pregnancy. This study was a prospective study involving 304 pregnant women with preeclampsia (n=152) and controls (non-preeclamptic pregnant women) (n=152). To investigate the rs2200287 and rs2148072 SNP's of TNFSF11 gene polymorphism by using the PCR-RFLP techniques. A significantly different genotype distribution of TNFSF11 (rs2200287 and rs2148072) polymorphisms were observed between the two groups, with the G allele of variant rs2200287 was highly significant in the preeclamptic group (P=0.000; .5814; OR=.5814; 95% CI=.4211-.8012). And the C allele of variant rs2148072 was also highly significant in the preeclamptic group (P=0.000; OR=.5076; 95% CI, .362-.71) in this study. The outcomes of the present study indicate that there was an association in TNFSF 11 (rs2200287 and rs2148072) gene polymorphism with preeclampsia compared to non-preeclampsia women.

AQUAPORIN-3 AND HEPARANASE GENETIC POLYMORPHISMS MAY MODULATE ANGIOGENESIS INFLUENCING THE RISK OF HYPERTENSIVE DISORDERS IN WOMEN

Objective: Preeclampsia (PE), a pregnancy complication triggered by oxidative stress and hypoxia, compromises mother and baby health and changes mother’s blood vessels increasing the risk for hypertension(HT). Aquaporin-3 (AQP3) is a water/H2O2/glycerol channel with implications in redox signaling. Heparanase (HPSE) has a role in extracellular matrix remodeling during angiogenesis. So far, no relation between AQP3 and HPSE genetic polymorphisms in PE subjects has been addressed. Thus, we aimed to investigate the association of AQP3(rs2231231) and HPSE(rs4693608) polymorphisms with the development of hypertensive disorders in women. Design and method: We investigated the distribution of AQP3 and HPSE genetic variations in a cohort of 150 normotensive (NT) or PE women, along with intermediate phenotype and anthropometric parameters. In a prospective study, women were reclassified 2–16 years after being PE or NT during pregnancy as NT or HT and genetic associations were reevaluated. Data was analyzed using SPSS software, P-values &lt; 0.05 were statistically significant. Results: No differences were found in the distribution of the studied polymorphisms in PE. Allele A of AQP3 was more prevalent in HT after pregnancy(P = 0.014) and correlated with subjects with increased systolic(P = 0.017) and diastolic(P = 0.008) blood pressures. Moreover, allele A was considered the allele of risk, associated with a 3.53-fold higher risk(P = 0.018) to develop HT after pregnancy. In this cohort, serum myeloperoxidase (MPO) higher levels correlated with PE (P = 0.000) and HT (P = 0.024) and were associated with HT after a NT pregnancy(P = 0.000). Although HPSE did not correlate with PE or HT, Allele A carriers were associated with increased Apolipoprotein A(ApoA;P = 0.027), uric acid(P = 0.027) and MPO(P = 0.005) in PE. In HPSE, PE subjects with allele G correlated with increased number of leucocytes(P = 0.048) while the presence of allele A was associated with decreased serum uric acid(P = 0.028). When the 4 groups were reevaluated, allele A of HPSE was associated with decreased blood glucose levels(P = 0.05) and increased pulse pressure(P = 0.003) and uric acid(P = 0.05) in women that had PE. Allele G was more frequent with lower levels of leucocytes(P = 0.024) in women that had PE and later HT. Conclusions: The AQP3 polymorphism is a promising biomarker for HT. HPSE polymorphism predicts PE-associated variations in the intermediate phenotype.

A review of key cytokines based on gene polymorphism in the pathogenesis of pre‐eclampsia

Although a number of theories have been suggested, including roles for oxidative stress, an abnormal maternal-fetal interface, and genetic and environmental factors, the etiopathology of pre-eclampsia (PE) remains unclear. Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years. The assessment of candidate genetic polymorphisms in PE could partially elucidate the mechanisms of susceptibility to disease, and contribute to seeking for new diagnosis and treatment methods of PE. PE can lead to severe complications, and even the death of both mother and fetus. Although the complex pathology is not yet clear, some evidence suggested that the occurrence of PE is related to inflammatory factors. We reviewed the current understandings of roles of cytokines in PE, and provided an extensive overview of the role of single nucleotide chain polymorphisms (SNPs) in the genes potentially underlying the pathophysiology of PE.

AQUAPORIN-3 AND CYBA GENETIC POLYMORPHISMS MAY PREDICT RISK OF DEVELOPING HYPERTENSION

Objective: Preeclampsia, a placentation disorder, affects 7% of pregnancies in Europe. It influences future cardiovascular disease, such as hypertension. Preeclampsia and hypertension have been associated with oxidative stress, therefore, key proteins in redox signaling may be involved with the development of hypertensive disorders during/after pregnancy. This study aimed at determining associations between oxidative stress-related gene polymorphisms (AQP3-rs2231231 and CYBA-rs4673) with the development of preeclampsia and the risk for future hypertension. Design and method: A cohort of 150pregnant Caucasian women, aged 35.24 ± 5.47 years, 60(40%) normotensive and 90(60%) preeclamptic, was evaluated. Based on a prospective study(2–16 years later), these women were evaluated for the development of hypertension and classified as normotensive 98(67%) or hypertensive 48(33%). The influence of genetic polymorphisms on the susceptibility for cardiovascular disease was evaluated. In this cohort, anthropometric/haemodynamic parameters were studied. For statistical analysis chi-square and Student t-test were used. Results: During pregnancy, no differences between the distribution of studied genetic polymorphisms in preeclampsia were found. However, based on the AQP3 dominant model of A, our data showed that AA+AC genotypes were more frequent (73.3%;p = 0.014) in hypertensive individuals. Moreover, allele A, the allele of risk, was associated with a 3.405-fold higher risk (p = 0.016,OR = 3.405,95%CI[1.26–9.19]) to develop hypertension after pregnancy. In addition, a higher systolic(p = 0.017) and diastolic(p = 0.008) pressure were also observed in women carrying the AA+AC genotype. Furthermore, based on CYBA dominant model of C, TT genotype of polymorphism was also correlated with the development of hypertension(100.0%;p = 0.007) after pregnancy. On the other hand, looking at the recessive model of C, CT+TT genotype was associated with the development of hypertension. Allele T, the allele of risk, was associated with 6.5-fold risk (p = 0,024,OR = 6.500,95%CI[1.28–33.03] to develop hypertension. Moreover, CT+TT genotypes of CYBA genetic polymorphism were more associated with increased weight (p = 0.014), higher waist circumference(p = 0.010), hip(p = 0.008) and systolic(p &lt; 0.001) and diastolic blood pressure(p &lt; 0.001). Conclusions: In this study, AQP3 genetic polymorphism was found associated with the hypertensive disorders after pregnancy for the first time. In addition, CYBA was also associated with the development of essential hypertension. These results open new perspectives in the development of new approaches for cardiovascular disease prevention.

Physiological predictions and the role of IL-10 -819 promoter polymorphism in preeclampsia

Preeclampsia is a multisystem pregnancy-specific syndrome that affects some of pregnancies, which remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Preeclampsia primarily provokes life-threatening, especially to the fetus. The aim of this study was to estimate some physiological and biochemical markers of preeclampsia and investigate the association between IL-10 -819 polymorphism and preeclampsia. A total of 52 pregnant women with preeclampsia and 35 women with normal pregnancy attended the high-risk unit of Erbil Maternity and Pediatric Governmental Hospital, KRG, Iraq, were considered in the present study. During the regular pregnancy check-ups, blood pressure, occurrence of gestational hypertension (early or late onset), preeclampsia, were also documented. Remarkably, serum Urea, Creatinine, Alkaline Phosphatase (ALP) and Mean Platelet Volume (MPV) were significantly increased in preeclampsia patients. In contrast, Direct Bilirubin, Glucose, GPT, GOT and Platelet count were not significant between preeclampsia and control women. Additionally, Mean Arterial Pressure (MAP) and Systolic Blood Pressure (SBP) were significantly elevated. Furthermore, genotyping of IL-10 T-819 C promoter polymorphism was carried out for all participants using a standard Amplification Refractory Mutation System (ARMS) PCR. Genotypic distribution of the control and patient groups were compared with values predicted by Hardy-Weinberg equilibrium using χ2 test. Interestingly, there were significant differences in (IL)-10 (-819) T/C genotype distribution frequency between preeclampsia and control groups. Conclusion The present study suggests that the IL-10 T-819 C gene promoter polymorphism might be a major genetic regulator in the etiology of increased risk of preeclampsia.

Plasma concentration of protein Z-dependent protease inhibitor and ZPI exon 3 mutations in preeclampsia

Protein Z-dependent protease inhibitor (ZPI) serves as a cofactor of inhibition of FXa and FXIa by protein Z. The levels of protein Z and polymorphisms have been shown in preeclampsia (PE) patients, but the plasma levels of ZPI and ZPI gene mutations were not reported yet. The principal aim of this study was to identify the concentration of ZPI and gene polymorphism in PE. ZPI levels were determined in 113 PE patients (age: 29.9 ± 3.9 years) and in 106 controls (normal pregnancy, age: 27.0 ± 2.8 years). ZPI was measured by enzyme-linked immunosorbent assay kit, and the gene polymorphism was determined by polymerase chain reaction and sequencing. The results showed ZPI antigen was found to be significantly lower in PE patients than in controls (ZPI, 1.24 ± 0.29 mg/L vs. 1.94 ± 0.35 mg/L, p < 0.05). The exon-3 missense mutations were distributed in patients and controls and there was no convincing correlation between these mutations and PE. It was of interest to observe a close relationship between the genotypes of the exon 3 polymorphisms 181 A > G and 481 A > T in the ZPI gene. Impact statement What is already known on this subject? The occurrence of PE is closely related to dysfunction of coagulation, and it is known that the decrease of PZ level can increase the occurrence probability of PE, while the polymorphism of PZ is not related to the occurrence of PE. As a cofactor of PZ, the content and polymorphism of ZPI which related to the occurrence of PE is worth further study. What the results of this study add? ZPI antigen was found to be significantly lower in PE patients than in controls, but there was no convincing correlation between exon-3 mutations and PE. What the implications are of these findings for clinical practice and/or further research? Our results support the view that ZPI plays a significant role in anticoagulant, and the genotype of the 181 gene polymorphism in exon-3 and 481 gene polymorphism in exon-3 are closely related. Other mutations like 435T > G(Phe145Leu), 972G > A(Trp324X), 1151A > G(Gln384Arg) are necessary to confirm the association between ZPI and prothrombotic state including PE.

A meta-analysis of the vascular endothelial growth factor polymorphisms associated with the risk of pre-eclampsia.

Backgroud: Pre-eclampsia (PE) is a common pregnancy-induced hypertension disease. Some case–control studies reported the association between vascular endothelial growth factor (VEGF) gene polymorphisms (rs3025039, rs2010963) and PE risk. However, these associations were inconsistent in several studies. Therefore, we conducted this meta-analysis to assess the role of VEGF gene polymorphisms in PE more precisely.Methods: Eligible studies were searched in PubMed, Embase, Web of Science and Chinese (Chinese National Knowledge Infrastructure (CNKI) and WanFang) databases. Statistical analyses were performed by Stata 12.0 software. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. In addition, subgroup analyses, sensitive analyses and publication bias analyses were performed to further assess this meta-analysis.Results: In total, 21 studies were included in the meta-analysis covering 2018 cases and 2632 controls. There were significant associations between VEGF polymorphisms (rs3025039, rs2010963) and PE risk in the overall populations. In the subgroup analyses, we found that rs3025039 polymorphism was associated with the increased risk of PE among Chinese. As for rs2010963 polymorphism, a significant association was observed in subgroup of Caucasian.Conclusion: The present study suggested that the two VEGF gene polymorphisms (rs3025039, rs2010963) are associated with increased risk of PE in different ethnic groups, which means that the targets may be useful genetic markers for early prediction of PE.

The role of two common FOXP3 gene promoter polymorphisms in preeclampsia in a Turkish population: a case–control study

Preeclampsia (PE), which occurs in approximately 5% of pregnancies worldwide and constitutes clinically serious complications in 2–3%, is one of the leading causes of maternal and prenatal morbidity and mortality. Recent studies report that regulatory T (Treg) cells, which act as immunosuppressant, are associated with PE. It is clearly defined that FOXP3/Scurfin (Forkhead Box P3) is involved in the development and function of Tregs. However, there are different conclusions regarding the relationship between PE and FOXP3 gene polymorphisms for different populations. For this reason, in this study we investigate the association between FOXP3 gene promoter region polymorphisms and PE in a Turkish population 500 PE patients and 500 healthy pregnant women. Blood samples taken from pregnant women were studied by PCR-RFLP method. As a result, rs2232365 polymorphism was significantly associated with disease (p < .0001) while no significant association was found between rs3761548 polymorphism and the disease (p = .17). Based on these results, it is though that FOXP3 rs2232365 polymorphism may be predisposed to PE development in terms of Turkish population. However, further and functional studies are needed in terms of other polymorphisms and mutations.IMPACT STATEMENTWhat is already known on this subject? A number of recent publications suggest that Tregs may play a role in the pathogenesis of PE. It is known that a stable and high FOXP3 expression is required to maintain the suppressive T cell function of Tregs. Down regulation of FOXP3 in PE has been reported in many previous studies, but the mechanism is still uncertain.What do the results of this study add? Our study has examined two FOXP3 promoter region polymorphisms in terms of Turkish population for the first time. Rs2232365 polymorphism associated with the disease in heterozygous genotype.What are the implications of these findings for clinical practice and/or further research? It has been shown that FOXP3 gene promoter region polymorphisms may be associated with PE for Turkish population. Our results can be a guide for more detailed statistical evaluations and functional studies.

Distribution of Polymorphisms of the Renin-Angiotensin System Genes (ACE, AGT, and AGTR1), ITGB3, and FTO in Pregnant Patients with Hypertensive Disorders.

The study included pregnant women aged 23-41 years with preeclampsia and gestation-associated arterial hypertension at weeks 27-40 and patients with essential arterial hypertension developing under conditions of the metabolic syndrome and without it. Frequency analysis of polymorphisms of the renin-angiotensin system genes (ACE, AGT, and AGTR1), ITGB3, FTO and their associations confirmed the syndrome nature of hypertensive disorders in pregnancy. The presence allele T of AGT gene and/or allele C of AGTR1 gene in the genotype of patients with preeclampsia was associated with higher BP and pressure load over 24 h. Allele D of ACE gene was also essential for BP parameters (pressure load) in patients with preeclampsia and gestation-associated arterial hypertension. Due to high genetic heterogeneity of the preeclampsia syndrome and genetic differences in the incidence of the studied gene polymorphisms in preeclampsia and gestation-associated arterial hypertension, no direct associations between these gestation disorders and polymorphic markers of the renin-angiotensin system genes can be established. However, polymorphisms of the renin-angiotensin system genes are essential for the 24-h dynamics of BP and pressure load under conditions of hypertensive disorders in pregnancy.

Investigation heme oxygenase-1 polymorphism with the pathogenesis of preeclampsia

ABSTRACTObjectives: The involvement of oxidative stress in the pathophysiology of preeclampsia (PE) has been already suggested. In this present study, we aimed to investigate the association of the genetic frequency of heme oxygense-1 (HMOX1) polymorphism with PE in Chinese Han women.Methods: We researched the genetic distribution of rs2071746 polymorphism in HMOX1 by the TaqMan allelic discrimination real-time PCR between 1235 PE patients and 1720 healthy women.Results: We found there were′t significant differences in the distribution of HMOX1 rs2071746 polymorphism in PE compared to the control group (rs2071746, genotype χ2 = 0.282, P = 0.869 and allele χ2 = 0.027, P = 0.869, OR = 1.009, 95% = 0.909–1.120).Conclusion: The rs2071746 polymorphism in HMOX1 might not be related to PE in Chinese women, although further investigations should be conducted to confirm our findings.

Circulating HO-1 levels are not associated with plasma sFLT-1 and GTn HMOX1 polymorphism in preeclampsia

ABSTRACTObjectives: We aimed to assess the plasma HO-1 level and its interrelationship with the plasma sFLT-1 level in preeclamptic and healthy pregnant women with different variants of microsatellite polymorphism (GTn) located in the promoter region of the HMOX-1 gene.Methods: HO-1 and sFLT-1 were measured by ELISA. HMOX1 genotyping was performed using fragment analysis.Results: We found similar and higher levels of plasma HO-1 and sFLT-1, respectively, in preeclampsia. Similar genotypes and alleles frequencies were found in both groups and the absence of modulation of HO-1 levels by genotypes were observed.Conclusion: The plasma HO-1 levels are not increased in preeclampsia women and neither related to sFLT-1 levels and GTn polymorphism.

VEGF and sFlt-1 polymorphisms in Preeclampsia

VEGF and sFlt-1 polymorphisms in Preeclampsia

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 Student's 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-10 -819(T/C) Promoter Polymorphism in Preeclampsia

Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive immune system. Interleukin-10 affects maternal intravascular inflammation, as well as endothelial dysfunction. The aim of the study was to investigate the association between IL-10 T-819 C polymorphism and preeclampsia. A total of 120 pregnant women with preeclampsia and 120 women with normal pregnancy attending the Gynecological Unit of Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system (ARMS) PCR was carried out for genotyping of IL-10 T-819 C promoter polymorphism in all the participants. Genotypic distribution of the control and patient groups was compared with values predicted by the Hardy-Weinberg equilibrium using χ2 test. Odds ratios (OR) and their respective 95 % confidence intervals were used to measure the strength of association between IL-10 gene polymorphism and preeclampsia. The frequencies of IL-10 T-819 C genotypes, CC, CT, and TT, were 47.5, 28.3, and 24.2 % in women with preeclampsia and 20.8, 48.3, and 30.8 % in the controls, respectively. There is a significant difference in the distribution of genotypes and alleles of IL-10 T-819 C between the two groups (test power = 0.66). The present study suggests that the IL-10 T-819 C gene promoter polymorphism can be a major genetic regulator in the etiology of preeclampsia.

Endothelial nitric oxide synthase (eNOS) (Glu298Asp) and urotensin II (UTS2 S89N) gene polymorphisms in preeclampsia: prediction and correlation with severity in Egyptian females

Background: Preeclampsia is a leading cause of maternal and fetal/neonatal morbidity and mortality. Early prediction of preeclampsia can minimize maternal and fetal complications. Gene polymorphisms are promising markers for early prediction of preeclampsia. Aim of work: To assess the value of endothelial nitric oxide synthase (eNOS) (Glu298Asp) and urotensin II (UTS2 S89N) gene polymorphisms for early prediction of preeclampsia. Methods: The preeclamptic group consisted of 53 pregnant who developed preeclampsia (35 mild and 18 severe), while the control group consisted of 65 age-matched pregnant females who completed uncomplicated pregnancies. eNOS and urotensin II gene polymorphisms were tested using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Results: Concerning the eNOS gene polymorphism, there were highly significant differences between the two groups regarding the GG genotype as well as the G and T allele frequency (p < 0.001) and a statistically significant differences regarding the GT, TT genotypes (p = 0.002, 0.0276, respectively). Concerning the urotensin II gene polymorphisms, there were highly significant differences regarding the SS, SN genotypes as well as the S and N allele frequency (p < 0.001), statistically significant differences regarding the NN genotype (p = 0.063). Conclusion: Women having mutation in any of the two studied genes are at risk to develop mild preeclampsia, and those having mutations in both genes are at risk to develop severe preeclampsia, while the females with normal pregnancy are protected by the higher percentage of expression of the normal (wild allelles) of both genes.

Update on genetics of pre-eclampsia

Over half of the familial predisposition to pre-eclampsia can be attributed to genetic factors in the mother and/or fetus. The search for genetic susceptibility variants has progressed through candidate gene studies, family-based linkage studies, and most recently genome-wide association studies (GWAS). It is unlikely that any single variant has a large effect on pre-eclampsia susceptibility; studies involving thousands of samples are required to detect variants with small effect size. These exceed the resources of most individual research groups, and collaborative approaches are likely to be more fruitful. Collaboration has included meta-analysis of existing data, and recent publications offer some support to a role for thrombophilic polymorphisms in pre-eclampsia. A small number of GWAS have been published so far; the lack of replication of positive GWAS results in an independent population has been frustrating. This may be due to false positive results in the original GWAS, or lack of statistical power in the replication set. A further concern is that the pre-eclampsia syndrome is a common end-point to multiple pathologies with differing underlying genetic susceptibility, requiring ever larger sample sizes for their detection. In this climate, researchers should make every effort to record the phenotypic characteristics of their cohorts, to enable meta-analysis of independent GWAS results. The InterPregGen consortium of groups from Europe and Central Asia is conducting GWAS analysis of maternal and fetal genes in 13,000 pre-eclamptic pregnancies. This study will provide the opportunity to analyse maternal-fetal gene interactions in addition to their individual effects. Developments arising from the ever-falling costs of DNA sequencing include deep sequencing to identify rare variants with large effect sizes. The era of whole genome sequencing is likely to supplant the GWAS approach, creating challenges for data analysis, but with the potential to provide greater insights into the genetic basis of pre-eclampsia.