Mihaela Iancu

Impact of demographic, genetic, and bioimpedance factors on gestational weight gain and birth weight in a Romanian population: A cross-sectional study in mothers and their newborns: the Monebo study (STROBE-compliant article).

AbstractThe present study had 2 objectives, first, to investigate possible relationships between increased gestational weight gain and demographic, clinical, paraclinical, genetic, and bioimpedance (BIA) characteristics of Romanian mothers, and second, to identify the influence of predictors (maternal and newborns characteristics) on our outcome birth weight (BW).We performed a cross-sectional study on 309 mothers and 309 newborns from Romania, divided into 2 groups: Group I—141 mothers with high gestational weight gain (GWG) and Group II—168 mothers with normal GWG, that is, control group.The groups were evaluated regarding demographic, anthropometric (body mass index [BMI], middle upper arm circumference, tricipital skinfold thickness, weight, height [H]), clinical, paraclinical, genetic (interleukin 6 [IL-6]: IL-6 -174G>C and IL-6 -572C>G gene polymorphisms), and BIA parameters.We noticed that fat mass (FM), muscle mass (MM), bone mass (BM), total body water (TBW), basal metabolism rate (BMR) and metabolic age (P < 0.001), anthropometric parameters (middle upper arm circumference, tricipital skinfold thickness; P < 0.001/P = 0.001) and hypertension (odds ratio = 4.65, 95% confidence interval: 1.27–17.03) were higher in mothers with high GWG. BW was positively correlated with mothers’ FM (P < 0.001), TBW (P = 0.001), BMR (P = 0.02), while smoking was negatively correlated with BW (P = 0.04). Variant genotype (GG+GC) of the IL-6 -572C>G polymorphism was higher in the control group (P = 0.042).We observed that high GWG may be an important predictor factor for the afterward BW, being positively correlated with FM, TBW, BMR, metabolic age of the mothers, and negatively with the mothers smoking status. Variant genotype (GG+GC) of the IL-6 -572C>G gene polymorphism is a protector factor against obesity in mothers. All the variables considered explained 14.50% of the outcome variance.

From Six Gene Polymorphisms of the Antioxidant System, Only GPX Pro198Leu and GSTP1 Ile105Val Modulate the Risk of Acute Myeloid Leukemia

Oxidative stress might contribute to the occurrence of cancers, including the hematological ones. Various genetic polymorphisms were shown to increase the quantity of reactive oxygen species, a phenomenon that is able to induce mutations and thus promote cancers. The purpose of the study was to evaluate the association between CAT C262T, GPX1 Pro198Leu, MnSOD Ala16Val, GSTM1, GSTT1, and GSTP1 Ile105Val gene polymorphisms and acute myeloid leukemia risk, in a case-control study comprising 102 patients and 303 controls. No association was observed between AML and variant genotypes of CAT, MnSOD, GSTM1, and GSTT1 polymorphisms. Our data revealed a statistically significant difference regarding the frequencies of GPX1 Pro198Leu and GSTP1 Ile105Val variant genotypes between AML patients and controls (p < 0.001). Our results showed no association in the distribution of any of the CAT C262T, GPX1 Pro198Leu, GSTM1, GSTT1, and GSTP1 polymorphisms regarding age, gender, FAB subtype, cytogenetic risk groups, FLT3 and DNMT3 gene mutations, and overall survival. Our data suggests that the presence of variant allele and genotype of GPX1 Pro198Leu and GSTP1 Ile105Val gene polymorphisms may modulate the risk of developing AML.

The contribution of clinical and pathological predisposing factors to severe gastro-duodenal lesions in patients with long-term low-dose aspirin and proton pump inhibitor therapy

BACKGROUND Preventive strategies developed to avoid the complications of antiplatelet therapies recommend the evaluation of risk factors for gastrointestinal events and indicated gastroprotective strategies. AIM We aimed to assess the impact of predisposing factors - histological findings, concomitant drug consumption, comorbidities, symptoms, social habits, Helicobacter pylori infection - on severe gastro-duodenal lesions in patients with low-dose aspirin and concomitant protective therapy with proton pump inhibitors (PPI). METHOD We enrolled 237 patients with LDA and PPI therapy, referred for upper digestive endoscopy, divided into two groups according to the severity of their endoscopic lesions (172 patients with no or mild endoscopic lesions and 65 patients with severe endoscopic lesions). RESULTS In the univariate logistic regression model, the factors associated with severe gastro-duodenal lesions were gender (OR=1.87, 95% CI: 1.04-3.41), anticoagulants (OR=2.40, 95% CI: 1.26-4.53), gastric atrophy and/or intestinal metaplasia (OR=1.85, 95% CI: 1.04-3.32), congestive heart failure (OR=2.59, 95% CI: 1.16-6.62), anaemia (OR=3.01, 95% CI: 1.67-5.47) and smoking (OR=4.29, 95% CI: 1.57-12.32). In the final model, anticoagulants (p=0.041<0.05) and anaemia (p=0.019<0.05) were risk factors for severe lesions via multivariate regression analysis, while for active/inactive chronic gastritis and smoking a positive dependency with a tendency towards statistical significance (p<0.10) was noticed for severe gastric lesions. CONCLUSIONS In patients treated with low-dose aspirin and gastroprotective therapy with proton pump inhibitors we have enough evidence to consider co-treatment with anticoagulants and anaemia important predictors for severe endoscopic lesions, while other factors such as inflammation in gastric biopsies, congestive heart failure, co-treatment with clopidogrel and smoking tended to have a positive influence on risk for severe gastro-duodenal lesions.

The FTO rs9939609 and LEPR rs1137101 mothers-newborns gene polymorphisms and maternal fat mass index effects on anthropometric characteristics in newborns: A cross-sectional study on mothers-newborns gene polymorphisms-The FTO-LEPR Study (STROBE-compliant article).

Abstract The aim of this study was to assess the impact of mothers’ and newborns’ fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs1137101 gene polymorphisms on neonatal anthropometric parameters in order to identify a potential risk for developing obesity. We performed a cross-sectional study on 355 mother–newborn couples in an Obstetrics Gynecology Tertiary Hospital from Romania, evaluated with regard to anthropometric parameters, clinical and laboratory parameters besides 2 genetic polymorphisms (FTO rs9939609 and LEPR rs1137101). Newborns with mothers carrying variant AT or AA genotype for FTO rs9939609 presented lower BMI (P = 0.012) and lower MUAC (P = 0.029). There was a significant interaction effect between newborn and mother LEPR rs1137101 polymorphism on birth weight (P = 0.009) and BMI (P = 0.007). We noticed significantly increased birth weight and BMI in newborns carriers of AG + GG genotype, coming from mothers with AA genotype (P = 0.006). There was no evidence of significant interaction effect between newborn and mother FTO rs9939609 polymorphism on the studied anthropometrical data (P > 0.05). In addition, lower BMI scores (P = 0.042) were observed in newborns carriers of TT genotype whose mothers had AA + AT genotype. Lower MUAC scores (P = 0.041) were noticed in newborns carriers of AA + AT genotype whose mothers had AA + AT genotype for FTO rs9939609 gene polymorphism. Newborns carriers of the AG + GG genotype (P = 0.003) of LEPR rs1137101 coming from mothers with increased FMI (upper tertile) had significantly increased BMIs. Presence of the variant A allele of FTO rs9939609 polymorphism in mothers decreased BMI and MUAC in newborns. The impact of LEPR rs1137101 polymorphism on BMI and birth weight in newborns differed depending on the presence/absence of the dominant LEPR allele in mothers. In addition, we noticed that maternal FMI presented a significant positive effect on newborns’ BMI by changing the effect of LEPR rs1137101. We can conclude that mothers’ FTO rs9939609 and LEPR rs1137101 gene polymorphisms presented an impact on birth weight and newborns’ BMI, therefore being involved in the newborns’ nutritional status and in the design of a potential protocol.

Clinical Risk Factors for Gastroduodenal Ulcer in Romanian Low-Dose Aspirin Consumers

Background. Aspirin use for cardiovascular or cancer prevention is limited due to its gastrointestinal side effects. Objective. Our prospective, observational case-control study aims to identify the predictive factors for ulcers in low-dose aspirin consumers (75–325 mg/day). Methods. The study included patients who underwent an upper digestive endoscopy and took low-dose aspirin treatment. Results. We recruited 51 patients with ulcer (ulcer group) and 108 patients with no mucosal lesions (control group). In univariate analysis, factors significantly associated with ulcers were male gender (p = 0.001), anticoagulants (p = 0.029), nonsteroidal anti-inflammatory drugs (p = 0.013), heart failure (p = 0.007), liver (p = 0.011) or cerebrovascular disease (p = 0.004), diabetes mellitus (p = 0.043), ulcer history (p = 0.044), and alcohol consumption (p = 0.018), but not Helicobacter pylori infection (p = 0.2). According to our multivariate regression analysis results, history of peptic ulcer (OR 3.07, 95% CI 1.06–8.86), cotreatment with NSAIDs (OR 8, 95% CI 2.09–30.58) or anticoagulants (OR 4.85, 95% CI 1.33–17.68), male gender (OR 5.2, 95% CI 1.77–15.34), and stroke (OR 7.27, 95% CI 1.40–37.74) remained predictors for ulcer on endoscopy. Conclusions. Concomitant use of NSAIDs or anticoagulants, comorbidities (cerebrovascular disease), and male gender are the most important independent risk factors for ulcer on endoscopy in low-dose aspirin consumers, in a population with a high prevalence of H. pylori infection.

Predicting functional outcome of ischemic stroke patients in Romania based on plasma CRP, sTNFR-1, D-Dimers, NGAL and NSE measured using a biochip array

In cerebral ischemia, evaluation of multiple biomarkers involved in various pathological pathways is a useful tool in assessing the outcome of the patients even from the early stages of the disease. In this study we investigated the utility of a panel of 5 peripheral biomarkers of inflammatory status, neuronal destruction and secondary fibrinolysis in the acute phase of ischemia, and evaluated the impact of these biomarkers on functional outcome after ischemic stroke. The 5 biomarkers (plasma CRP, D-Dimers, sTNFR-1, NGAL and NSE) were measured using a biochip array technology. Eighty nine patients in Romania were divided into 2 subgroups using the modified Rankin Scale evaluated at 3 months after ischemic stroke; the possible impact of analyzed biomarkers on unfavorable functional outcome was tested by binomial logistic regression. The subgroup with unfavorable outcome had higher concentrations of CRP, NGAL, sTNFR-1 and D-dimers, but CRP and NGAL values were not statistically different between the two subgroups. The univariate logistic regression analysis of plasma biomarkers revealed that CRP, D-Dimers, NGAL, sTNFR-1 were significant predictors of unfavorable clinical outcome. In the case of D-Dimers and sTNFR-1 we noticed an increased discrimination ability (versus baseline clinical model) to classify poor functional outcome with a tendency toward statistical signification. During the acute phase of the ischemic stroke, plasma concentrations of CRP, D-Dimers and sTNFR-1 were elevated in unfavorable outcome patients. D-Dimers and sTNFR-1 were independent predictors of poor outcome at 3 months after ischemic stroke. The biochip array technology offers the possibility to simultaneously measure several parameters involved in multiple pathophysiological pathways, in a small sample volume.

The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk

The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20–4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19–3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72–4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00–2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37–0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

The role of TGF-β1 869 T > C and PPAR γ2 34 C > G polymorphisms, fat mass, and anthropometric characteristics in predicting childhood obesity at birth: A cross-sectional study according the parental characteristics and newbornʼs risk for child obesity (the newborns obesityʼs risk) NOR study

Abstract This study proposed to establish a correlation between the risk score for child obesity and anthropometric, genetic, and bioimpedance characteristics in mothers and newborns, and to assess the discriminant ability for anthropometric parameters to classify over-fatness (defined by bioimpedance body fatness %) in pregnant women. We performed a cross-sectional study on 388 couples (mother and father) and their newborns admitted in a Tertiary Hospital from Romania. The measured parameters for mothers and their newborns were risk percentage for child obesity, anthropometric characteristics (mid-upper arm circumference [MUAC], tricipital skinfold thickness [TST] of mother and newborn), genetic polymorphisms (human peroxisome proliferator-activated receptor γ [PPARγ2] 34 C > G and transforming growth factor-beta 1 [TGF-β1] 869 T > C gene polymorphisms in both mothers and newborns), and mothers bioimpedance characteristics (fat mass [FM] %). The obesity risk score according to standard predictable Northern Finland Birth Cohort equation was in our study 4.07%. We found a monotone positive significant correlation between the newborns risk of childhood obesity and the mothers TST (P = 0.01), as well as a tendency toward statistical significance concerning correlation with mothers MUAC (P = 0.053), without any correlations with the mothers’ bioimpedance parameters and also a positive correlation between the newborns risk of childhood obesity and the newborns anthropometrical characteristics like body mass index (BMI), MUAC, and TST (P < 0.001). We observed that the calculated newborns risk percentage for child obesity was greater for the variant allele of the TGF-β1 869 T > C polymorphism and also for the wild-type C allele of the PPARγ2 34 C > G gene polymorphism. Our study indicated that the best predictors for over-fatness are BMI and MUAC (P = 0.01 < 0.02 and P = 0.019 < 0.02, respectively).