FAST and Agile-the MASLD drift: Validation of Agile 3+, Agile 4 and FAST scores in 246 biopsy-proven NAFLD patients meeting MASLD criteria of prevalent caucasian origin.

BACKGROUND: MASLD is a prevalent chronic liver condition with substantial clinical implications. This study aimed to assess the effectiveness of three new, elastography-based, scoring systems for advanced fibrosis ≥F3 (Agile 3+), cirrhosis F4 (Agile 4), and fibrotic NASH: NASH + NAS ≥4 + F≥2 (FAST score), in a cohort of biopsy-proven NAFLD meeting MASLD criteria. Our secondary aim was to compare their diagnostic performances with those of other fibrosis prediction tools: LSM-VCTE alone, and common, easily available scores (FIB-4 or APRI). METHODS: Single-center, retrospective study, on consecutive patients with baseline laboratory tests, liver biopsy, and reliable LSM-VCTE measurements. The discrimination between tests was evaluated by analyzing the AUROCs. Dual cut-off approaches were applied to rule-out and rule-in ≥F3, F4 and fibrotic NASH. We tested previously reported cut-off values and provided our best thresholds to achieve Se ≥85%, Se ≥90%, and Sp ≥90%, Sp ≥95%. RESULTS: Among 246 patients, 113 (45.9%) were women, and 75 (30.5%) presented diabetes. Agile 3+ and Agile 4 demonstrated excellent performance in identifying ≥F3 and F4, achieving AUROCs of 0.909 and 0.968, while the FAST score yielded acceptable results in distinguishing fibrotic NASH. When compared to FIB-4 and LSM-VCTE, both Agile 3+ and Agile 4 performed better than FIB-4 and had a similar performance to LSM-VCTE, but with higher diagnostic accuracy, hence reducing the grey zone. CONCLUSION: Agile 3+ and Agile 4 are reliable, non-invasive tests for identifying advanced fibrosis or cirrhosis in MASLD patients, while FAST score demonstrates moderate performance in identifying fibrotic NASH.

TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

From Innate Immunity to Metabolic Disorder: A Review of the NLRP3 Inflammasome in Diabetes Mellitus.

The role of the NLRP3 inflammasome is pivotal in the pathophysiology and progression of diabetes mellitus (DM), encompassing both type 1 (T1D), or type 2 (T2D). As part of the innate immune system, NLRP3 is also responsible for the chronic inflammation triggered by hyperglycemia. In both conditions, NLRP3 facilitates the release of interleukin-1ß and interleukin-18. For T1D, NLRP3 perpetuates the autoimmune cascade, leading to the destruction of pancreatic islet cells. In T2D, its activation is associated with the presence of insulin resistance. NLRP3 activation is also instrumental for the presence of numerous complications associated with DM, microvascular and macrovascular. A considerable number of anti-diabetic drugs have demonstrated the ability to inhibit the NLRP3 inflammasome.

How to Identify Advanced Fibrosis in Adult Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) Using Ultrasound Elastography-A Review of the Literature and Proposed Multistep Approach.

Non-alcoholic fatty liver disease (NAFLD), and its progressive form, non-alcoholic steatohepatitis (NASH), represent, nowadays, real challenges for the healthcare system. Liver fibrosis is the most important prognostic factor for NAFLD, and advanced fibrosis is associated with higher liver-related mortality rates. Therefore, the key issues in NAFLD are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. We critically reviewed the ultrasound (US) elastography techniques for the quantitative characterization of fibrosis, steatosis, and inflammation in NAFLD and NASH, with a specific focus on how to differentiate advanced fibrosis in adult patients. Vibration-controlled transient elastography (VCTE) is still the most utilized and validated elastography method for liver fibrosis assessment. The recently developed point shear wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) techniques that use multiparametric approaches could bring essential improvements to diagnosis and risk stratification.

Association of Parental Factors and Insulin-like Growth Factor 2 Polymorphism with Intrauterine Growth Restriction.

Polymorphism of insulin-like growth factor 2 (IGF2) is known to play a role in cell development. Only the paternal IGF2 copy is active, while the copy inherited from the mother is inactive. This study aimed to explore whether maternal and paternal factors influence IGF2 polymorphism in newborns with intrauterine growth restriction (IUGR) compared to appropriate for gestational age (AGA). A cross-sectional exploratory study was conducted from June 2014 to November 2015 at the Neonatology, Gynecology 1 Clinic, Cluj-Napoca, Romania. The ApaI IGF2 genotypes and allele frequencies were similar in the IUGR and AGA groups (p-value > 0.10). The IUGR babies with a protective IGF2 genetic profile had significantly younger parents (a difference in the median age of 8 years for mothers and 9 years for fathers; p-value < 0.009). The IUGR babies had parents with lower birth weights than AGA babies (mothers' medians: 2800 g vs. 3100 g; fathers' medians: 3000 g vs. 3400 g; p-value < 0.02). In univariable regression analysis, the mother's and father's birth weight proved to be associated with IUGR. The father's birth weight proved to be the only factor significantly associated with IUGR, independent of the mother's birth weight or the presence of a protective IGF2 genetic profile (odd ratio = 0.998 [0.996 to 1.000], p-value = 0.032).

Polymorphisms of Vitamin D Receptor and the Effect on Metabolic and Endocrine Abnormalities in Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age. Vitamin D and its receptor are thought to play an important role in PCOS susceptibility, although the impact of vitamin D receptor (VDR) polymorphisms on the hormonal and metabolic profile is still controversial. A literature search in PubMed and Embase was performed up to September 2020 for case-control studies in women suffering from PCOS, with outcome related to VDR polymorphisms effect on metabolic/endocrine disturbances. We have found 16 eligible studies including 2566 women with PCOS and 2430 controls. ApaI polymorphism seemed to be associated with hyperandrogenism in both Asian and Caucasian population. FokI variant was correlated with metabolic/endocrine parameters especially in Asian population, while a relation between Cdx2 genotypes and insulin sensitivity was observed in both ethnicities. VDR polymorphisms have an important role in PCOS development and related hormonal and metabolic abnormalities. Few case-control studies analysed the interaction between VDR variants and metabolic/endocrine parameters with the majority of the articles focused on the Asian region. Further research on various ethnic populations with larger sample size are still needed for a definitive conclusion, in order to allow early diagnosis and prevention of PCOS comorbidities.

Association between polymorphisms of genes involved in the Renin-Angiotensin-Aldosterone System and the adaptive morphological and functional responses to essential hypertension.

Hypertensive cardiac remodeling is illustrated by increased left ventricular (LV) mass index values and/or relative wall thickness (RWT) values >0.42, and functionally by isolated alteration of LV diastole (abnormal relaxation). The aim of the present study was to establish differentiated models of anatomical and functional adaptation to essential hypertension (EHT), in relation to the genetic variants of genes involved in the Renin-Angiotensin-Aldosterone System (RAAS). The M235T-AGT, I/D-ACE, A1166C-R1AngII, A3123C-R2AngII and G83A-REN genotypes were determined using PCR-Restriction Fragment Length Polymorphism in 139 hypertensive subjects. The relationship between the studied RAAS gene polymorphisms with morphological and functional cardiac remodeling was assessed by multiple logistic regression analysis. Patients carrying the C/C, A/C genotypes (A3123C-R2AngII polymorphism) had a 2.72-fold (P=0.033) increased risk of exhibiting an RWT value <0.42; in the multivariate model the risk was 4.02-fold higher (P=0.008). Analysis of LV diastolic dysfunction (LVDD) revealed that hypertensive patients carrying the T/T, M/T genotypes (M235T-AGT polymorphism) had a 2.24-fold (P=0.037) increased risk of developing LVDD and a 2.42-fold increased risk (P=0.039) after adjustment for confounders. Similarly, carriers of the G/G, A/G genotypes (G83A-REN) had a 2.32-fold (P=0.021) increased risk of developing LVDD, and this remained an independent risk factor based on the multivariate model (P=0.033). The results of the present study showed that no particular gene was associated with increased LV mass, but the A3123C-R2AngII polymorphism was associated with a non-concentric type of cardiac response in hypertensive patients. Conversely, the M235T-AGT and G83A-REN polymorphisms were found to be statistically significantly associated with LVDD when assessing abnormal relaxation.

Association Between M235T-AGT and I/D-ACE Polymorphisms and Carotid Atheromatosis in Hypertensive Patients: A Cross-Sectional Study.

BACKGROUND/AIM: The renin-angiotensin-aldosterone system (RAAS) may be implicated in carotid atheromatosis (CA) development. We aimed to assess the relationship of M235T-angiotensinogen (AGT) and insertion/deletion of angiotensin conversion enzyme (I/D-ACE) genotypes with CA in patients with essential hypertension (EHT). PATIENTS AND METHODS: We determined the M235T-AGT and I/D-ACE genotypes, using PCR-RFLP methods, in 162 hypertensive subjects from three tertiary regional medical centers. The relationship between the studied RAAS gene polymorphisms and CA was assessed by multiple logistic regressions. RESULTS: Hypertensive patients carrying the MT/TT235-AGT and MT235-AGT genotypes had a 2.17-fold (p=0.033) and 2.24-fold (p=0.036) increased risk to develop CA, respectively. These genotypes, MT/TT 235-AGT (OR=2.17, p=0.033) and MT235-AGT (OR=2.24, p=0.036), remain independent risk factors for CA in hypertensive patients according to the multivariate model. CONCLUSION: There is a statistically significant association between M235T-AGT and CA, when adjusting for several confounders and controlling for hypertension.

Vitamin D and the insulin-like growth factor system: Implications for colorectal neoplasia.

Epidemiological studies have strongly associated lower levels of vitamin D and its metabolites with an increased risk of colorectal cancer (CRC). The action of calcitriol, the active metabolite of vitamin D, is mediated by the vitamin D receptor (VDR) that is present in most tissues. In advanced CRC, VDR expression is lowered. Calcitriol has several antineoplastic effects in CRC: it promotes the G1-phase cycle arrest, lowers vascular endothelial growth factor (VEGF) synthesis and acts on tumour stromal fibroblasts to limit cell migration and angiogenesis. Hyperinsulinemia and insulin-like growth factors (IGFs) have been implicated in the pathophysiology of CRC. IGF-1 and IGFBP-3 have been the most studied components of the IGF system. Only 1% of the total serum IGF-1 is free and bioactive, and 80% of it binds to IGFBP-3. IGF-1 and its receptor IGF-1R are known to induce cell proliferation. Both IGF-1 and IGFBP-3 can favour angiogenesis by increasing the transcription of the VEGF gene. A high serum IGF-1/IGFBP-3 ratio is associated with increased risk for CRC. VDR is a transcription factor for the IGFBP-3 gene, and IGF-1 can increase calcitriol synthesis. Studies examining the effect of vitamin D treatment on serum IGF-1 and IGFBP-3 have not been in agreement since different populations, dosages and intervention periods have been used. New vitamin D treatment studies that examine CRC should take in account confounding factors such as obesity or VDR genotypes.

Renin-angiotensin system gene variants and risk of early- and late-onset preeclampsia: A single center case-control study.

BACKGROUND: Changes in the renin-angiotensin-aldosterone system's (RAAS) activity due to different genetic variations could represent risk factors for the onset of preeclampsia. OBJECTIVE: To test and quantify the relationships of 8 RAAS gene polymorphisms (angiotensinogen (AGT)-M235T, AGT-T174M, angiotensin converting enzyme (ACE)-I/D, ACE8-A2350G, angiotensin II type 1 receptor (AGTR1)-A1166C, angiotensin II type 2 receptor (AGTR2)-C3123A, renin (REN)-G83A, aldosterone synthase (CYP11B2)-T344C) with susceptibility to early- (EOPE) and late-onset preeclampsia (LOPE). STUDY DESIGN: We performed polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) analysis in 217 pregnant women, of whom 87 pregnant women with EOPE/LOPE and 130 normal pregnant women. The relationship between the studied RASS gene polymorphisms and EOPE/LOPE was tested by multiple logistic regressions. RESULTS: The multivariate logistic regression analysis showed that AGT-M235T (adjusted OR = 4.63), AGT-T174M (adjusted OR = 4.13), REN-G83A (adjusted OR = 3) and CYP11B2-C344T (adjusted OR = 3.13) gene polymorphisms remained independent risk factors for EOPE. Moreover, ACE-I/D (adjusted OR = 4.04), ACE-A2350G (adjusted OR = 3.5), AGTR1-A1166C (adjusted OR = 2.73), and REN-G83A (adjusted OR = 2.67) polymorphisms remained independent risk factors for LOPE. The frequency of overweight was significantly different (p = 0.001) in pregnant women with EOPE, LOPE and the control group (LOPE:16, 29.6% vs. EOPE:12, 36.4% vs. control group:16, 12.3%). Pregnant women with EOPE had babies with a significantly lower mean birth weight (2067.9 ±â€¯887.9) in comparison to women with LOPE (mean ±â€¯SD: 2860.1 ±â€¯771.1, p < 0.001) and women with normal pregnancies, respectively (mean ±â€¯SD: 3324.9 ±â€¯484.9, p < 0.001). CONCLUSION: We confirmed the influence of the renin-angiotensin-aldosterone system through these 8 genetic variations on the onset of preeclampsia.

Serum levels and ApaI polymorphism of insulin-like growth factor 2 on intrauterine growth restriction infants.

PURPOSE: The aim of our study was to evaluate the IGF2 and IGF2R plasmatic level and IGF2-ApaI polymorphism on infants with intrauterine growth restriction (IUGR). MATERIALS AND METHODS: A transversal study was conducted at the Neonatology Ward of the Gynecology Clinic I, Emergency Hospital Cluj-Napoca on neonates with IUGR who were discharged during June 2014 and June 2015. The serum levels of IGF2 and IGF2R were obtained by using ELISA method and IGF2-ApaI polymorphism by taking PCR-RFLP analysis. RESULTS: Forty infants with IUGR and 21 infants of appropriate gestational age (AGA) were evaluated. The serum levels of IGF2 proved higher on the A/G genotype when the IUGR group was compared with AGA (p value = .048). The G allele proved significantly more frequent in both the IUGR and the AGA group compared with the A allele (p < .002). Neither any allele nor any genotype proved a risk factor for IUGR (p value > .3). The A/G genotype proved significantly more frequent on term infants compared with preterm infants (p value = .039). CONCLUSIONS: The infant with IUGR has a higher serum level of IGF2 if has A/G IGF2-ApaI genotype and higher values of IGF2R if it has the A/A genotype.

D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

AIM: To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. MATERIALS AND METHODS: We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. RESULTS: Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. CONCLUSION: The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

Newborn APOE genotype influences maternal lipid profile and the severity of high-risk pregnancy - preeclampsia: Interaction with maternal genotypes as a modulating risk factor in preeclampsia.

AIM: To establish the role of the interaction between maternal and newborn apolipoprotein E (APOE) genotypes on the risk, lipid profile and prognosis of preeclampsia (PE). MATERIALS AND METHODS: Forty-seven preeclamptic women and 94 normotensive pregnant women and their newborns were genotyped for APOE using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Maternal APOE-ε4 allele was associated with an about eight times higher risk of PE (adjusted OR = 8.4, 95% CI: 2.51-28.17, p = 0.001). The multivariate logistic regression model showed that the newborn APOE-ε4 allele was associated with an about six times higher risk of PE (adjusted OR = 5.6, 95% CI: 2.09-15.21, p = 0.001) for the given gestational age levels. Pregnant women with severe PE whose newborns carried the APOE-ε4 allele delivered at earlier gestational ages neonates with a lower birth weight compared to pregnant women with newborns negative for this allele. Higher TG and LDL-C levels and lower HDL-C levels were found in pregnant women with severe PE whose newborns were carriers of the APOE-ε4 allele compared to preeclamptic women whose newborns were carriers of the ε3/ε3 genotype. If we checked the combined effect of the mother/newborn genotypes on the risk of PE, we found that the risk to develop PE was 15.4-fold (p < 0.001) increased if mothers or newborns were carriers of the APOE-ε4 allele. The risk increased to 20.02 (p < 0.001) if both the mother and newborn were carriers of the APOE-ε4 allele. CONCLUSIONS: Our study confirms the maternal/newborn APOE genotype interaction influences the risk for PE, as well as prognosis and lipid profile.

Maternal/newborn VEGF-C936T interaction and its influence on the risk, severity and prognosis of preeclampsia, as well as on the maternal angiogenic profile.

OBJECTIVE: To analyze the influence of maternal/newborn vascular endothelial growth factor (VEGF)-CT936 interaction as a modulating factor in preeclampsia as well as its influence on the maternal angiogenic balance. METHODS: Seventy pairs of preeclamptic women/newborns and 94 pairs of normal pregnant mothers/newborns were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum VEGF and soluble VEGF receptor-1 (sVEGFR-1) levels were measured using ELISA. RESULTS: The risk to develop mild (odds ratio; OR: 3.79, p = 0.008) and severe (OR: 2.94, p = 0.037) preeclampsia being increased in association with the CT936-VEGF genotype and increased in severe preeclampsia to 6.07 (p = 0.03) if the women were carriers of the homozygous TT936-VEGF genotype. The presence of the VEGF-T936 allele in both the mother and the newborn significantly increases the risk of pregnancy-induced hypertension (PIH), mild and severe preeclampsia. If both the mothers and newborns were carriers of the VEGF-T936 allele, significantly lower VEGF and higher sVEGFR-1 levels were observed for all types of preeclampsia. Pregnant women with PIH and severe preeclampsia delivered at a significantly earlier gestational age neonates with a significantly lower birth weight if both the preeclamptic mothers and their newborns were carriers of the VEGF-T936 allele. CONCLUSIONS: Our study suggests the role of maternal/fetal VEGF-CT936 polymorphism as a modulating factor in preeclampsia, which affects the angiogenic balance in preeclamptic mothers, as well as their pregnancy outcome.

GSTM1-null genotype as a risk factor for sporadic colorectal cancer in a Romanian population. Association with the NAT2-rapid-acetylator phenotype and exposure to environmental factors.

We evaluated the association between the presence of the GSTM1-null genotype and the combined presence of the GSTM1-null genotype/NAT2 rapid acetylator phenotype and the risk of developing sporadic colorectal cancer (CRC), as well as their interaction with environmental risk factors. One hundred and fifty patients with sporadic CRC and 162 controls were genotyped using PCR-RFLP analysis. For testing and quantification of the simple effect (main effect) and of the gene-gene and gene-environment interaction (modification effect), univariate and multivariate logistic regression was used. In the multiplicative model, from the genetic factors, GSTM1-null and NAT2*6B had a statistically significant influence on the risk for CRC, while from the environmental factors, smoking and diet had similar effects. The combination of GSTM1-null/NAT2 rapid acetylator phenotype/smoking behavior or GSTM1-null/NAT2 rapid acetylator phenotype/diet rich in fried red meat was not found to influence the sporadic CRC risk in Romanians, but the GSTM1-null genotype, NAT2 rapid acetylator phenotype influenced the sporadic CRC risk differently depending on the gender of the patient.

LPL Ser447Ter and Asn291Ser variants in Romanians: associations with preeclampsia - implications on lipid profile and prognosis.

OBJECTIVES: To investigate the role of LPL-Ser447Ter and Asn291Ser polymorphisms in the predisposition to different types of preeclampsia, as well as the contribution to the lipid profile and the prognosis of preeclampsia. METHODS: 125 women with preeclampsia and 131 normal pregnant women were genetically screened using PCR-restriction enzyme analysis. RESULTS: We found an increased risk for mild and severe preeclampsia in carriers of the negative Ser447/Ser447 genotype. An increased risk for severe preeclampsia in carriers of the Asn291Ser polymorphism was seen. In mild and severe preeclampsia, carriers of the negative Ser447/Ser447 genotype had increased TG and LDL-C levels and decreased HDL-C levels as compared with carriers of the Ser447Ter polymorphism. The presence of the Asn291Ser polymorphism influenced the higher TG and LDL-C levels and the lower HDL-C levels in mild preeclampsia and the higher TG and LDL-C levels in severe preeclampsia. Women with severe preeclampsia, carriers of the Ser447/Ser447 genotype and women with mild preeclampsia, carriers of the Asn291Ser polymorphism, delivered at a lower gestational age neonates with a lower birth weight compared to women carriers of this polymorphism. CONCLUSIONS: The LPL variants are associated with severe preeclampsia and influence the lipid profile and pregnancy outcome in mild and severe preeclampsia.

The Ala-9Val (Mn-SOD) and Arg213Gly (EC-SOD) polymorphisms in the pathogenesis of preeclampsia in Romanian women: association with the severity and outcome of preeclampsia.

OBJECTIVE: To check whether individual or combined mutated genotypes for Ala-9Val (Mn-SOD) and Arg213Gly (EC-SOD) are associated with preeclampsia; to check the influence of the mutated genotypes on the degree of severity and perinatal outcome of preeclampsia. METHODS: We genotyped 97 pregnant women (47 with preeclampsia and 50 normal pregnant women) using PCR-RFLP analysis. RESULTS: The Val/Val (Mn-SOD) genotype (OR 5.99, p = 0.004) but not the Gly/Gly (EC-SOD) genotype (OR 4.23, p = 0.027) was significantly associated with preeclampsia. Higher frequency of both polymorphisms in women with preeclampsia (42.55%) compared to normal pregnant women (8%). Higher frequency of women diagnosed with PIH (27.27%, OR 4.31), mild (50%, OR 11.5) and severe preeclampsia (37.5%, OR 6.9) positive for both polymorphism compared to control women (8%). There was a statistically significant difference in gestational age at delivery according to Mn-SOD (Ala/Ala vs. Val/Val, 39 ± 1.41 weeks vs. 32.77 ± 3.7 weeks) and EC-SOD genotypes (Arg/Arg vs. Gly/Gly, 37.05 ± 3.18 weeks vs. 31.5 ± 3.84 weeks). There also was a statistically significant difference in birth weight according to Mn-SOD (grams, Ala/Ala vs. Val/Val, 3080 ± 481.66 vs. 2376.92 ± 916.88) and EC-SOD genotypes (grams, Arg/Arg vs. Gly/Gly, 2934.09 ± 662.14 vs. 2080 ± 721.19). CONCLUSIONS: Our study demonstrates a relationship between these two mutated genes, the clinical severity and the perinatal outcome of preeclampsia.

Maternal/newborn genotype contribution of the renin-angiotensin system (Met235Thr, Thr174Met, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A- AT2R2, 83A/G-REN) to the risk of pre-eclampsia: a Romanian study.

INTRODUCTION: We evaluated the association of the mutated genotypes Met235Thr-AGT, Thr174Met-AGT, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A-AT2R2, (83)A/G-REN with the risk and outcome of pre-eclampsia; we also investigated whether genes in newborns increase maternal risk of pre-eclampsia. MATERIALS AND METHODS: Thirty-six pairs of pre-eclamptic women and their newborns were genotyped, along with 71 pairs of controls (mothers/newborns) using PCR-RFLP analysis. RESULTS: The Thr235/Thr235 (OR 3.44, p = 0.01), DD (OR 2.66, p = 0.039), CC1166 (OR 5.56, p = 0.04), AA3123 (OR 3.77, p = 0.03) and GG(83) (OR 8.32, p = 0.006) genotypes are significantly associated with pre-eclampsia. Women with pre-eclampsia positive for Met235Thr (34.64 ± 3.92 weeks vs. 38 ± 2 weeks), Thr174Met (32.58 ± 3.92 weeks vs. 36.38 ± 3.25 weeks), I/D (34.47 ± 3.67 weeks vs. 38.33 ± 3.5 weeks) delivered at a significant lower gestational age compared with pre-eclamptic women with a normal genotype. Newborns from women with pre-eclampsia positive for Thr174Met (2190 ± 820.21 g vs. 2702.08 ± 967.23 g), I/D (2399.33 ± 938.38 g vs. 3191.66 ± 684.40 g) had a significant lower birth weight compared with newborns from women with normal pregnancies. When both the mother and the newborn were positive for Met235Thr, I/D, A2350G, A1166C or (83)A/G polymorphisms, the risk for pre-eclampsia was significantly increased at 6.67 (p < 0.01), 5 (p < 0.01), 3.33 (p = 0.006), 2.72 (p = 0.04) and 7.8 (p < 0.01), respectively. CONCLUSIONS: The results of our study confirm that, in pre-eclampsia, both maternal and newborn genetic variations implicated in blood pressure regulation are important.

Correlation between the TSHRc-Asp727Glu polymorphism and plasma thyroid stimulating hormone levels in Romanian preeclamptic women.

AIM: To analyze the influence of thyroid stimulating hormone (TSH) levels and/or the Asp727Glu polymorphism on the severity and perinatal outcome of preeclampsia. METHODS: Forty-nine women with preeclampsia and 58 normal pregnant women were genotyped for the TSHRc-Asp727Glu polymorphism using PCR-RFLP methods. The plasma TSH levels were measured by ELISA method. RESULTS: Fourteen (77.78%) women of 18 pregnant women with abnormal TSH levels had preeclampsia compared to 35 (39.33%) of 89 pregnant women with normal TSH levels who had preeclampsia (OR 5.4, p = 0.003). The mean TSH levels were 2.13 ± 1.44 µU/ml, 2.47 ± 2.03 µU/ml and 4.27 ± 2.75 µU/ml in women with pregnancy induced hypertension (PIH), mild and severe preeclampsia, respectively. OR for PIH and mild preeclampsia was 1.08 (p = 1) and 9.45 (p = 0.06), respectively, in association with the Asp/Asp genotype. All women with severe preeclampsia had the Asp/Asp genotype. The risk for preeclampsia in association with TSH > 4 µU/ml and Asp/Asp genotype is 20.8 (p < 0.01). Preeclamptic women with TSH levels > 4 µU/ml and the Asp/Asp genotype delivered earlier (weeks, 34.92 ± 4.33 vs. 36.6 ± 3.21, p = 0.3) neonates with lower birth weight (grams, 2361.54 ± 1155.81 vs. 3000 ± 1072.38, p = 0.3) than preeclamptic women with TSH levels  < 4 µU/ml and the Asp/Glu genotype. CONCLUSIONS: Higher TSH levels and/or the TSHRc-Asp727Glu polymorphism represent risk factors for preeclampsia and could be correlated with the severity of preeclampsia.