Assessment of matrix metalloproteinase (MMP)-2, MMP-8, MMP-9, and their inhibitors,the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in obese children and adolescents

ObjectivesTo compare the circulating levels of matrix metalloproteinase (MMP)-8, pro-MMP-2, pro-MMP-9, and total MMP-9, their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2, and the MMP-8/TIMP-1, MMP-9/TIMP-1, and MMP-2/TIMP-2 ratios in normotensive obese children and adolescents with those found in non obese children and adolescents.Design and methodsWe studied 40 obese and 40 non obese (controls) children and adolescents in this cross-sectional study. MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA.ResultsObese children and adolescents had higher circulating MMP-8 concentrations, lower plasma TIMP-1 concentrations, and higher MMP-8/TIMP-1 ratios than non obese controls (P < 0.05). We found no differences in pro-MMP-9 or total MMP-9 levels, or in MMP-9/TIMP-1 ratios between groups (P > 0.05). While we found no significant differences in pro-MMP-2 levels (P > 0.05) obese subjects had higher TIMP-2 concentrations and lower pro-MMP-2/TIMP-2 ratios (P < 0.05) than non obese controls.ConclusionsIn conclusion, we found evidence indicating higher net MMP-8 (but not MMP-9 and MMP-2) activity in childhood obesity. The increased MMP-8 levels found in obese children suggest a possibly relevant pathophysiological mechanism that may be involved in the increase of cardiovascular risk associated with childhood obesity.     

Matrix metalloproteinase (MMP)-9 genotypes and haplotypes in preeclampsia and gestational hypertension

BackgroundAbnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. We examined whether 2 MMP-9 polymorphisms (C^? 1562 T and (CA)n) and haplotypes are associated with preeclampsia and/or gestational hypertension.MethodsWe studied 476 pregnant women: 176 healthy pregnant (HP), 146 pregnant with gestational hypertension (GH), and 154 pregnant with preeclampsia (PE). Genomic DNA was extracted from whole blood and genotypes for C^? 1562 T and (CA)n polymorphisms were determined by PCR-RFLP. Haplotype frequencies were inferred using the PHASE ver. 2.1 program.ResultsFor the g.?90(CA)13–25 polymorphism, no significant differences were found in genotype and allele distributions when PE or GH groups were compared with HP group. However, the CT genotype and T allele for g.?1562C > T polymorphism were more commonly found in GH subjects compared with the HP group (both P < 0.05). Conversely, we found no differences in genotypes or allele distributions for the g.?1562C > T polymorphism when the PE and the HP groups were compared. No significant differences were found in overall distributions of haplotype frequencies when the GH or the PE group was compared with the HP group.ConclusionsThe C^? 1562 T polymorphism in MMP-9 gene is associated with gestational hypertension, but not with preeclampsia. These findings may help to explain the higher plasma MMP-9 levels previously reported in GH compared with HP.     

Increased inflammatory response and imbalance in blood and urinary oxidant-antioxidant status in South Indian women with gestational hypertension and preeclampsia

ObjectiveThe objective of this study is to assess the association of blood and urinary oxidative stress parameters and inflammatory markers in women with gestational hypertension and preeclampsia.Design and methodsMalondialdehyde, protein bound sialic acid and C-reactive protein were estimated in serum and urine of pregnant women diagnosed with preeclampsia (n = 30) and gestational hypertension (n = 30) and the results were compared with 30 normal pregnant women.ResultsWhole blood glutathione level was reduced, and malondialdehyde and C-reactive protein levels were significantly higher and correlated with each other in preeclampsia (p < 0.05). Urinary malondialdehyde significantly correlated with urinary protein bound sialic acid in preeclampsia (r = 0.412; p = 0.02). Receiver operating curve analysis of serum protein bound sialic acid and serum malondialdehyde showed reasonable cutoff values for the differential diagnosis of preeclampsia.ConclusionsOxidative stress and inflammatory response are greater in women with preeclampsia in comparison to pregnant women with gestational hypertension and there is an association between oxidative stress and inflammatory response.     

Serum MMPs and TIMPs: May be predictors of breast carcinogenesis?

BackgroundThe involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in breast cancer has been documented on palpable lesions. This study aims to assess serum MMP1, MMP-2, TIMP-1, and TIMP-2 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specifically in non-palpable mammographic breast lesions.MethodsOn women with benign (n = 65), precursor [ADH (n = 18) and LN (n = 15)], preinvasive [DCIS (n = 32)] and invasive [IDC (n = 28)] lesions the serum concentrations of MMP-1, MMP-2, TIMP-1, TIMP-2, TPS, and TPA were determined with immunoenzymatic assays. All women had non-palpable mammographic breast lesions of less than 10 mm in diameter, as estimated on the mammographic views. Statistical analysis followed.ResultsTIMP-2 serum concentrations were positively associated with the severity of the lesion. On the contrary, MMP-2 levels were marginally negatively associated with severity; as evident, the MMP-2/TIMP-2 ratio significantly decreased along with severity. Regarding TIMP-1, TPS, TPA, and TIMP-1/TIMP-2, no significant associations were demonstrated. MMP-2 and the MMP-2/TIMP-2 ratio were significantly higher in the LN subgroup versus the ADH subgroup.ConclusionTIMP-2 and MMP-2/TIMP-2 ratio may exhibit meaningful changes along with progression of lesions. Extracellular cell matrix remodeling in ductal and lobular lesions may follow distinct patterns.     

ADAMTS13, FVIII, von Willebrand factor, ABO blood group assessment in preeclampsia

IntroductionPreeclampsia (PE) is a multifactorial disease characterized by high blood pressure and proteinuria after the 20th week of pregnancy. PE is associated with fibrin deposition in placental microcirculation and intrauterine fetal growth retardation. We evaluated FVIII activity, VWF and ADAMTS13 plasma levels, according to O and “non O” blood groups, in women with severe PE (sPE).MethodsThis case-control study included 140 women; 55 pregnant with sPE, 35 normotensive pregnant and 50 non-pregnant women. VWF and ADAMTS13 antigen levels were assessed by ELISA (American Diagnostica). FVIII activity was measured by automated coagulometric method (Dade Behring) and ABO blood groups phenotyping was performed by indirect technique.ResultsFVIII activity and VWF levels were significantly higher comparing either sPE to normotensive pregnant (P = 0.01; P = 0.05) and to non-pregnant women (P = 0.00 in both cases) or normotensive pregnant and non-pregnant women (P = 0.00 in both cases). A significant decrease in ADAMTS13 levels was observed comparing either sPE to normotensive pregnant (P = 0.02) and non-pregnant women (P = 0.00) or normotensive pregnant and non-pregnant women (P = 0.00). FVIII activity and VWF levels were associated to O and “non O” blood groups only in non-pregnant women.ConclusionsThe increase of FVIII activity and VWF levels and the decrease of ADAMTS13 in sPE are not associated to O and “non O” blood groups. These alterations in hemostatic markers in sPE largely surpass those physiologically determined by ABO blood groups influence and may have masked the effect of O and “non O” groups in this disease. A concomitant analysis of VWF levels and ADAMTS13 activity and antigenic levels will be important to clarify the imbalance between these parameters found in sPE in the present study.     

Serum heat shock protein 70 levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in women with preeclampsia

BackgroundWe have previously reported that serum levels of 70 kDa heat shock protein (Hsp70, HSPA1A) are increased and reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. The purpose of this study was to determine whether increased serum Hsp70 concentrations in women with preeclampsia are related to circulating levels of cytokines, chemokines, adhesion molecules and angiogenic factors, the key players in the pathogenesis of the disease.MethodsSixty preeclamptic patients and 60 normotensive, healthy pregnant women were involved in this case-control study. Levels of Hsp70 (HSPA1A) and transforming growth factor (TGF)-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex suspension array. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were measured by electrochemiluminescence immunoassay. For statistical analyses, the Mann–Whitney U-test, the Fisher exact and Pearson chi-square tests, the Spearman rank order correlation, multiple linear regression and logistic regression were applied.ResultsSerum levels of Hsp70 were significantly higher in preeclamptic patients than in healthy pregnant women. Additionally, most of the measured inflammatory variables differed significantly between the two study groups except for serum IL-1beta and TGF-beta1 levels and IL-18/IL-12p70 and IL-12p70/IL-12p40 ratios, indicating a bias toward a pro-inflammatory status in preeclampsia. Preeclamptic patients had significantly higher sFlt-1 levels and sFlt-1/PlGF ratio and significantly lower PlGF concentrations as compared to healthy pregnant women. In the preeclamptic group, serum Hsp70 concentrations showed significant correlations with serum levels of IL-12p40 (R = 0.59, p < 0.001), MCP-1 (R = 0.43, p < 0.001), ICAM-1 (R = 0.39, p = 0.0020) and VCAM-1 (R = 0.46, p < 0.001). Furthermore, elevated serum Hsp70 level and sFlt-1/PlGF ratio had a synergistic (joint) effect in the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone.ConclusionsIncreased serum Hsp70 concentrations in women with preeclampsia were associated with pro-inflammatory changes in circulating cytokine profile, suggesting that circulating Hsp70 might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease.     

Anticoagulants affect matrix metalloproteinase 9 levels in blood samples of stroke patients and healthy controls

ObjectivesMatrix metalloproteinase-9 (MMP-9) represents a promising marker for acute stroke management. In clinical studies MMP-9 has been quantified by ELISA using differing protocols. We aimed to establish a valid protocol by evaluation of preanalytics.Design and methodsBlood from stroke patients (n = 28) and healthy controls (n = 28) was drawn into tubes containing different anticoagulants (EDTA, citrate, lithium-heparin (heparin) and heparin with proteinase inhibitors) and processed after 0, 60 and 240 min. MMP-9 plasma protein and mRNA from mononuclear leukocytes were determined.ResultsIn regard to anticoagulants used, samples showed different MMP-9 protein baseline values and kinetics. Stable MMP-9 protein concentrations were only measured from EDTA samples. Particularly in samples with proteinase inhibitors protein and mRNA concentrations increased over time. Kinetics did not differ between patients and controls.ConclusionsPreanalytics plays a key role for determination of MMP-9. EDTA seems to be a valid anticoagulant for MMP-9 protein measurement.     

Serum autotaxin measurements in pregnant women: application for the differentiation of normal pregnancy and pregnancy-induced hypertension

BackgroundThe bioactive lipid lysophosphatidic acid (LPA) exerts multiple effects in the female reproductive system. Serum/plasma LPA is mainly produced by the lysophospholipase D activity of autotaxin (ATX). Previous studies have suggested that ATX has critical roles in cancer, reproduction, and vascular development. In the present study, we evaluated the usefulness of serum ATX measurements in pregnant women.MethodsWe measured the serum ATX antigen levels in 32 normal pregnant women, 15 patients with pregnancy-induced hypertension (PIH), and 7 patients with preterm delivery using a recently developed automated enzyme immunoassay.ResultsThe serum ATX antigen levels in normal pregnant women were significantly higher than those in non-pregnant women (P < 0.001). The serum ATX antigen levels in normal pregnant women were significantly and positively correlated with the gestational week (r = 0.809, P < 0.001). During the third trimester, the serum ATX antigen levels of the patients with PIH (3.299 ± 1.720 mg/l) were significantly lower than those of the normal pregnant women (4.915 ± 2.323 mg/l) (P = 0.04).ConclusionsThe serum ATX antigen level increases with the progression of pregnancy. The serum ATX level may be a serological marker for the prediction of PIH.     

Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus

ObjectivesMatrix metalloproteinases (MMPs) are suggested to play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study is to examine the MMPs expressions and activities in Taiwanese RA and SLE patients.Design and methodsLevels and activities of plasma MMP-2 and MMP-9 were investigated by enzyme-linked immunosorbent assay and zymography, respectively.ResultsMMP-2 levels in control subjects, RA and SLE patients were 146.1 ± 34.2, 194.0 ± 24.2 and 208.9 ± 75.9 ng/mL respectively, and for MMP-9 were 51.4 ± 57.1, 567.7 ± 313.1 and 208.7 ± 105.5 ng/mL respectively. Both MMP-2 and MMP-9 levels and activities from all patients were significantly higher than that from control subjects.ConclusionsMMP-2 levels in both patients groups were approximately 1.3–1.4 folds higher than that in control subjects, notably, MMP-9 levels were 11- and 4-folds significantly higher, respectively, in RA and SLE patients. The results which MMP-2 and MMP-9 levels and activities are significantly elevated support the involvement of MMPs proteins in these autoimmune disorders.     

Matrix metalloproteinase 9 gene haplotypes affect left ventricular hypertrophy in hypertensive patients

BackgroundMatrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients.MethodsWe studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C^? 1562T (rs3918242), ? 90 (CA)_14–24 (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters.ResultsMMP-9 ? 90 (CA)_14–24 “HH” genotype (H allele defined by number of CA repeats ≥ 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (“C, H, Q”) protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (“T, H, Q”, P = 0.0015 and P = 0.0057, respectively).ConclusionGenetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients.     

Role of serum matrix metalloproteinase-2 and -9 to predict breast cancer progression

ObjectiveMatrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been reported as putative tumor markers because of their involvement in cancer invasion and metastasis. The aim of our study was to elucidate the possible role of MMP-2 and -9 as serum prognostic biomarker for breast cancer classification and correlate it with the clinicopathological variables.Design and MethodsOur study consisted of 60 females with primary breast cancer, 40 cases of benign breast disease and 60 healthy female volunteers as controls. The serum MMP-2 and -9 levels were quantitatively measured by ELISA technique.ResultsA significantly raised MMP-2 and MMP-9 levels were observed in breast cancer patients. Significant rise in serum MMP-9 concentration was found in patients presenting with metastasis as well as in those cases who presented with a duration of less than 1 year. ROC analyses depicted a serum cutoff value of 315 ng/mL for MMP-9 to discriminate the breast cancer patients from the control group.ConclusionOur results suggest that serum MMP-9 level is a better marker than serum MMP-2 in predicting the breast cancer development and progression.     

Natriuretic peptide precursor B gene (TTTC)(n) microsatellite polymorphism in pre-eclampsia

BackgroundThere is a variable tandem repeat polymorphism in the 5′-flanking region of the natriuretic peptide precursor B gene (NPPB). A previous study showed association of the (TTTC) small tandem repeat (STR) variants of this gene and essential hypertension. Our aim was to identify this polymorphism in samples of pre-eclamptic patients and healthy controls. We also compared the natriuretic peptide B (BNP) concentrations.MethodsBlood samples were collected from healthy pregnant normotensive women (n = 235) and women with pre-eclampsia (n = 220). DNA was isolated and fluorescent PCR and DNA fragment analysis was performed for the detection of (TTTC) repeats. The plasma BNP concentration was measured by fluorescence immunoassay method.ResultsWe detected 12 different (TTTC) repeats on the NPPB gene in the studied population. The overall distribution of alleles and genotypes was significantly different between the control and pre-eclamptic groups. The number of 10-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnant controls (p = 0.032). After adjustment for confounding factors pre-pregnancy BMI, maternal age, primiparity and smoking, the calculated odds ratio (OR) was 0.19 (95% CI: 0.04–0.87). Similarly, the 12-repeat genotype carriers showed significantly lower frequency in pre-eclamptics than in the healthy pregnants (p = 0.037; adjusted OR: 0.53 (95% CI: 0.29–0.96)). In contrast the 11-repeat genotype carrier frequency was significantly higher in the pre-eclamptic than in the healthy pregnant group (p < 0.001; adjusted OR 2.91 (95% CI: 1.75–4.84)).The concentration of the BNP was 9.75 pg/ml in the healthy controls and 32.40 pg/ml in the pre-eclamptic group (p < 0.0001). The 11/11 genotype carriers had significantly higher BNP levels in both groups.ConclusionsThe NPPB gene (TTTC) microsatellite polymorphism in the 5′-flanking region showed significant difference in the distribution of alleles and genotypes between healthy pregnant controls and pre-eclamptic patients in an ethnically homogeneous population. The concentration of the BNP was higher in pre-eclamptic women, and it showed association with the (TTTC) genotypes. We introduced an F-PCR and DNA fragment analysis method for the fast and reliable detection of this STR.     

Peripheral blood level alterations of MMP-2 and MMP-9 in patients with chronic kidney disease on conservative treatment and on hemodialysis

ObjectivesData concerning the levels of metalloproteinase-2 (MMP-2) and MMP-9 in uremia and dialysis are conflicting and incomplete.Design and methodsWe measured the serum MMP levels in patients with chronic kidney disease (CKD) and undergoing maintenance hemodialysis (HD), and we tried to identify factors that could affect their levels.ResultsMMP-2 and the high sensitivity C-reactive protein (hsCRP) were inversely correlated with hematological parameters in the whole CKD group. CKD patients with stages 3 + 4 showed a significant increase in the MMP-9 levels compared to the other studied groups; this metalloproteinase was inversely correlated with lymphocyte count, and positively correlated with the hsCRP. The MMP-2 levels were higher in pre and post HD patients compared to the control group and CKD stage 1 + 2. In contrast, there was no difference in the MMP-9 levels. Both MMP-2 and MMP-9 were associated with the leukocyte count in pre HD group.ConclusionsThis study suggests a connection between an inflammatory state, biochemical response and the MMP levels in uremic and dialysis patients.     

Evaluation of metalloproteinases 2 and 9 and their inhibitors in physiologic and pre‐eclamptic pregnancy

Matrix metalloproteinases (MMPs) are a family of zinc and calcium‐dependent endopeptidases involved in remodeling and physiological homeostasis of extracellular matrix (ECM). The metalloproteinases activity is predominantly modulated by specific tissue inhibitors of matrix metalloproteinases (TIMPs). The balance between MMPs and TIMPs is likely to play an important role in remodeling uterine arteries in pregnancy, and it may represent means by which vasodilatation is maintained in later pregnancy. Moreover, increased levels of MMPs and in particular MMP‐2 play a role in the vascular alterations induced by hypertension. The aim of this study was the evaluation of MMP‐2 and ‐9, along with their inhibitors TIMP‐1 and ‐2, in pre‐eclamptic women compared with normotensive pregnancy and non‐pregnant women. Fourteen pre‐eclamptic women were compared with 37 normotensive women in different gestational age and 21 non‐pregnant women. Multiplexed sandwich enzyme‐linked immunosorbent assay was used to measure MMPs and TIMPs simultaneously. MMP‐2 levels were significantly higher in pre‐eclamptic women vs. both non‐pregnant and physiologic pregnant women. MMP‐9 concentrations were significantly higher in physiologic pregnant vs. non‐pregnant women. The serum levels of TIMP‐1 were significantly higher in pre‐eclamptic vs. both non‐pregnant and physiologic pregnant women. TIMP‐2 values were higher in physiologic pregnant women and pre‐eclamptic women vs. non‐pregnant women. A positive correlation between MMP‐9 values and gestational age was observed in normal pregnant women. Results of the present investigation confirm that MMP‐2 and TIMP‐1 values are significantly higher in preeclampsia. We confirm that the modification of the fine balance between MMPs and their inhibitors plays a greater role in the structural and functional vascular changes of women with complicated pregnancies. J. Clin. Lab. Anal. 23:88–92, 2009. © 2009 Wiley‐Liss, Inc.     

Healthy Moms, a randomized trial to promote and evaluate weight maintenance among obese pregnant women: study design and rationale

BackgroundObesity and excessive weight gain during pregnancy are associated with adverse pregnancy outcomes. Observational studies suggest that minimal or no gestational weight gain (GWG) may minimize the risk of adverse pregnancy outcomes for obese women.ObjectiveThis report describes the design of Healthy Moms, a randomized trial testing a weekly, group-based, weight management intervention designed to help limit GWG to 3% of weight (measured at the time of randomization) among obese pregnant women (BMI ≥ 30 kg/m²). Participants are randomized at 10–20 weeks gestation to either the intervention or a single dietary advice control condition.Primary outcomesThe study is powered for the primary outcome of total GWG, yielding a target sample size of 160 women. Additional secondary outcomes include weight change between randomization and one-year postpartum and proportion of infants with birth weight > 90th percentile for gestational age. Statistical analyses will be based on intention-to-treat.MethodsFollowing randomization, all participants receive a 45-minute dietary consultation. They are encouraged to follow the Dietary Approaches to Stop Hypertension diet without sodium restriction. Intervention group participants receive an individualized calorie intake goal, a second individual counseling session and attend weekly group meetings until they give birth. Research staff assesses all participants at 34-weeks gestation and at 2-weeks and one-year postpartum with their infants.SummaryThe Healthy Moms study is testing weight management techniques that have been used with non-pregnant adults. We aim to help obese women limit GWG to improve their long-term health and the health of their offspring.     

Association between the -2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and hypertension in Tunisian patients

ObjectivesMonocyte chemoattractant protein-1 (MCP-1:CCL2) has been demonstrated to be involved in the pathophysiology of atherosclerosis and hypertension. This study was aimed to investigate whether the single nucleotide polymorphism (SNP) at ?2518 of the MCP-1 gene promoter region is associated to hypertension in a sample of Tunisian population.Design and methodsA total of 290 Tunisian patients with hypertension and 390 normotensive controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsA significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 7.2% for the GG genotype, 35.2% for the AG genotype and 57.6% for the AA genotype. Normotensive subjects had a frequency of 3.6% for the GG genotype, 29.7% for the AG genotype and 66.7% for the AA genotype (χ² = 8.02, p = 0.01). The hypertension patient group showed a significant higher frequency of the G allele compared to the controls [0.24 vs. 0.18; OR (95%CI), 1.46 (1.11–1.91), p = 0.004]. The association between the ?2518 G/A polymorphism of MCP-1 gene and hypertension remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionThe present study showed a significant and independent association between the ?2518G/A polymorphism of the MCP-1 gene (presence of G allele) and hypertension in the Tunisian population.     

Serum Retinol-Binding Protein 4 (RBP4) and retinol in a cohort of borderline obese women with and without gestational diabetes

ObjectivesTo evaluate whether serum RBP4 correlates with gestational diabetes mellitus (GDM) in a cohort of borderline obese (BMI > 30) pregnant women.Design and methodsSerum RBP4 and retinol were measured in pregnant women with (n = 12) and without (n = 10) GDM.ResultsRBP4, retinol and RBP4:retinol molar ratio were not different between the groups and were not associated with markers of insulin resistance.ConclusionsGDM is not associated with RBP4 or retinol among borderline obese pregnant women.     

MMP-2 and TIMP-2 gene polymorphisms and susceptibility to atrial fibrillation in Chinese Han patients with hypertensive heart disease

BackgroundMMP-2 and TIMP-2 play important roles in the pathogenesis of arrhythmogenic atrial remodeling, and may contribute to the development and persistence of atrial fibrillation (AF). Functional polymorphisms in the promoter of MMP-2 and TIMP-2 gene may modulate an individual's susceptibility to AF.MethodsA total of 881 hypertensive heart disease patients from Chinese Han population (128 with and 753 without AF) were recruited in this study. The genotypes of the MMP2-1306C>T and -735C>T polymorphisms and TIMP-2 -418G>C polymorphisms were determined using PCR based method. The plasma concentration of TIMP-2 was measured by enzyme-linked immunosorbent assay in a subgroup with 81 patients.ResultsBoth genotype distribution and allele frequency of the TIMP-2 -418G>C polymorphism were significantly different between the AF and control group (P = 0.005 and P = 0.001, respectively). The C allele carriers (GC + CC) had a significantly increased risk of AF compared with the GG homozygotes (odds ratio,1.77, 95% CI 1.21–2.92, P = 0.009) in a logistic regression model after adjustment for age, left atrial dimension, left ventricular mass index, and antihypertensive drugs. The C allele carriers also had reduced levels of plasma TIMP-2 levels compared with GG homozygotes in both AF patients and control subjects. No relationship was found in this cohort between the presence of the MMP-2 -1306C>T and -735C>T polymorphism and AF.ConclusionsThe TIMP-2 -418G>C polymorphism is significantly associated with an increased susceptibility to AF in Chinese Han patients with hypertensive heart disease. The -418C allele, which is associated with a decreased expression of TIMP-2, might be a genetic risk for the development of AF in this cohort.     

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

BackgroundPlasma activities of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase, and γ-glutamyl transferase (GGT) are often increased in cardiometabolic diseases. We investigated if hypertension is associated with increased activities of these plasma markers.MethodsWe included 235 hypertensive and 708 normotensive subjects (mean age 47.3 ± 9.6 and 58.0 ± 10.2 years respectively) from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000–2004 who had drank < 1/week. In the follow-up study in 2005–2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension.ResultsRaised plasma ALT (OR = 1.22 per SD of log-transformed level, P = 0.045) and GGT (OR = 1.38 per SD of log-transformed level, P = 0.001) levels were associated with hypertension at baseline in CRISPS-2 after adjusting for covariates. Among subjects not on anti-hypertensive medications, plasma ALP, ALT and GGT were related to blood pressure (P < 0.01). In subjects normotensive at CRISPS-2, plasma GGT, but not ALP, ALT and AST, was an independent predictor of new-onset hypertension at CRISPS-3 (OR = 1.38 per SD of log-transformed level, P = 0.020 and OR = 2.68 for 3rd tertile vs. 1st tertile, P = 0.004) after adjusting for covariates.ConclusionsAmong the 4 plasma markers, increased GGT activity is the strongest predictor for existing and new-onset hypertension in Hong Kong Chinese.     

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of myocardial infarction among Tunisian male patients

ObjectivesThe aim of the present study was to investigate the association between CCR2-Val64Ile and CCR5-Δ32 variants and the estimation of haplotypes with MI in a sample of the Tunisian population.Design and methodsA total of 290 unrelated MI patients and 282 healthy controls were studied. The CCR2-Val64Ile and CCR5-Δ32 variants were analyzed by PCR-RFLP.ResultsSubjects carrying at least one copy of the CCR5-deletion allele were significantly more common in the control group, suggesting an atheroprotective effect (adjusted OR = 0.44, 95% CI = 0.28–0.72, p = 0.001). Haplotype analysis showed that MI patients had significantly less 64Val-Del haplotype (9.9% vs. 21.3%, OR = 0.30, 95% CI = 0.21–0.43, p < 0.001) and 64Ile-Ins haplotype (12.3% vs. 16.7%, OR = 0.58, 95% CI = 0.42–0.80, p < 0.001).ConclusionA protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.