Opposite effects of GSTM1 -and GSTT1 - gene deletion variants on bone mineral density

Abstract. Oxidative stress is associated with osteoporosis. The glutathione S-transferases form the major detoxifying group of enzymes responsible for eliminating products of oxidative stress. We have therefore proposed GSTM1 and GSTT1 genes as candidates for studying the genetics of osteoporosis. The aim of the present study was to examine possible association of GSTM1 and GSTT1 gene deletion polymorphisms, alone or in combination, with bone mineral density at femoral neck (BMD fn), lumbar spine (BMD ls) and total hip (BMD th) in Slovenian elderly women and men. GSTM1 and GSTT1 gene deletion polymorphisms in 712 elderly people were analyzed using the triplex PCR method for the presence of GSTM1 and GSTT1 gene segments. BMD fn, BMD ls and BMD th were measured by the dual-energy X-ray absorptiometry (DEXA) method. Results were analyzed using univariate statistic model adjusted for sex, body mass index (BMI) and age. Our results showed the significant differences in BMD th, BMD ls and BMD fn values (p = 0.031, 0.017 and 0.023, respectively) in subgroups of GSTT1 gene deletion polymorphism. For GSTM1 gene deletion polymorphism borderline significant association was found with BMD ls (p = 0.100). Furthermore, subjects with homozygous deletion of GSTT1 gene showed higher BMD values on all measured skeletal sites and, in contrast, subjects with homozygous deletion of GSTM1 gene showed lower BMD values. Moreover, a gene-gene interaction study showed significant association of GSTM1-null and GSTT1-null polymorphisms with BMD ls values (p = 0.044). Carriers with a combination of the presence of GSTT1 gene and the homozygous absence of GSTM1 gene fragment were associated with the lower BMD values at all skeletal sites. The significant association of combination of GSTT1 gene presence and homozygous absence of GSTM1 gene with BMD was demonstrated, suggesting that it could be used, if validated in other studies, as genetic marker for low BMD

Correlation between cerebral biomarkers and optic nerve sheath diameter in patients with severe preeclampsia

Objective: To examine the correlation between plasma cerebral biomarkers (S100B and neuron-specific enolase (NSE)) and ultrasonographic optic-nerve-sheath-diameter (ONSD) in preeclampsia. Methods: Thirty preeclampsia patients and 27 controls were included. Mann-Whitney-U test was used for comparison of S100B, NSE, and ONSD in preeclampsia vs. controls. Kendall’s tau was used to assess the correlation between biomarkers and ONSD (p < 0.05 significant). Results: ONSD, S100B and NSE were significantly higher in preeclampsia (p < 0.001, p = 0.004, and p < 0.001, respectively). There was significant correlation between NSE levels and ONSD: Kendall’s tau = 0.26; p = 0.01. Conclusions: S100B and NSE are elevated in severe preeclampsia. NSE correlates with increased ONSD suggesting cerebral edema

Correlation between uterine artery Doppler and the sFlt-1/PlGF ratio in different phenotypes of placental dysfunction

Objective: To explore correlations between the sFlt-1/PlGF ratio and uterine arteries (UtA) Doppler indexes in placental dysfunction-related disorders (PDD). Methods: We prospectively included women with a singleton pregnancy with preeclampsia (PE) only (n = 22), preeclampsia with fetal growth restriction (FGR) (n = 32), FGR only (n = 12), or normal pregnancy (n = 29). Results: In PDDs, significantly positive correlations between the sFlt-1/PlGF ratio and the mean UtA pulsatility (mPI-UtA), as well as the resistance index (mRI-UtA) were found (p = 0.015, p = 0.019, respectively), but not in normal pregnancies. PDD with signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio and mPI-UtA, was found in 50.0%, and, by the increased sFlt-1/PlGF ratio and mRI-UtA, in 65.2%. PDD without signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio but normal mPI-UtA, was found in 24.2%, and, by the increased sFlt-1/PlGF ratio but normal mRI-UtA, in 7.6%. A substantial proportion of women with signs of impaired placentation were diagnosed with FGR with or without PE. Conclusion: In PDD, the sFlt-1/PlGF ratio and UtA Doppler indexes increase proportionally. Correlations between the sFlt-1/PlGF ratio and UtA Doppler indexes might help to distinguish between PDDs with and without impaired placentation. However, further studies are needed to explore the correlations in different phenotypes of PDD

Biophysical Markers of Suspected Preeclampsia, Fetal Growth Restriction and The Two Combined—How Accurate They Are?

Objectives—To conduct a secondary analysis of prediction accuracy of biophysical markers for suspected Preeclampsia (PE), Fetal Growth Restriction (FGR) and the two combined near delivery in a Slovenian cohort. Methods—This was a secondary analysis of a database of a total 125 Slovenian pregnant women attending a high-risk pregnancy clinic due to suspected PE (n = 31), FGR (n = 16) and PE + FGR (n = 42) from 28–39 weeks gestation and their corresponding term (n = 21) and preterm (PTD, n = 15) controls. Data for Mean Arterial blood Pressure (MAP) and Uterine artery pulsatility index (UtA PI) estimated by Doppler sonography were extracted from the database of patients who were tested at admission to the high-risk clinic with the suspected complications. The reactive hyperemia index (RHI), and the Augmentation Index (AIX%) were extracted from the patient database using measured values obtained with the assistance of the Endo PAT, a device set to measure the signal of the peripheral arterial tone (PAT) from the blood vessels endothelium. Linear regression coefficients, Box and Whisker plots, Area under the Curve (AUC) of receiver Operation Characteristic (ROC) curves, and multiple regression were used to assess the marker accuracy using detection rate (DR) and false-positive rate (FPR) and previously reported cut-offs for estimating the positive and negative predictive value (NPV and PPV). The SPSS non-parametric statistics (Kruskal Wallis and Mann–Whitney) and Spearman’s regression coefficient were used to assess marker accuracy; p 0.6 for UtA Doppler PI over GA for PE and FGR, whereas for RHI over BMI, the regression coefficient was r > 0.5 (p p < 0.001), especially in cases of FGR. Conclusion—The classical biophysical markers MAP and UtA Doppler PI provided diagnostic accuracy for PE and FGR < 34 wks gestation. A multiple biophysical marker analysis was required to reach diagnostic accuracy for all cases of these complications. The UtA Doppler PI and maternal serum sFlt-1/PlGF or PlGF were equally accurate for early cases to enable the choice of the markers for the clinical use according to the more accessible method

Blood cadmium, mercury, and lead in children: An international comparison of cities in six European countries, and China, Ecuador, and Morocco

Children's blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 mu g/L) and B-Pb (14-20 mu g/L), but larger for B-Hg (0.12-0.94 mu g/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 mu g/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city children's B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe. (C) 2011 Elsevier Ltd. All rights reserved

Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco

Objectives: The aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (BPb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants. Materials and Methods: About 50 women (age: 46–62) from each city were recruited (totally 480) in 2006–2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation. Results: Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5–27.0 μg/l and 0.25–0.65 μg/l, respectively); the variation of B-Hg was larger (0.40–1.38 μg/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2–68.0, 0.39–0.99 and 1.01–2.73 μg/l, respectively. Smoking was a statistically signifi cant determinant for B-Cd, while fi sh and shellfi sh intakes contributed to B-Hg and B-Pb, amalgam fi llings also contributed to B-Hg. Conclusions: The present results confi rm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confi rms the previous fi ndings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is signifi cant