Association between myeloperoxidase polymorphisms and its plasma levels with severity of coronary artery disease

ObjectivesMyeloperoxidase (MPO) polymorphism ?463 has been related to higher cardiovascular risk. This study was conducted to test whether the MPO promoter polymorphism ?463A/G and MPO plasma levels are associated with coronary artery disease (CAD) severity.Design and methodsPatients submitted to elective coronariography were enrolled, CAD severity was assessed and blood samples collected to identify the MPO polymorphism and its plasma levels.ResultsGenotypes were determined in 118 patients. Among these patients, 12 (10%) were homozygous for AA, 69 (58%) for GG and 37 (32%) were heterozygous. Mean MPO plasma levels were 8.6 ± 4.7 ng/mL for AA, 8.6 ± 7.0 ng/mL for AG and 9.4 ± 5.6 ng/mL for GG genotypes. The CAD severity was not associated with MPO genotypes (p = 0.43), however, patients with higher CAD score presented higher MPO levels (p = 0.02).ConclusionWe found no association between MPO polymorphism and CAD severity, although a relation was observed for MPO plasma levels and extension of CAD.     

Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a Chinese population

ObjectiveCoronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methionine sulfoxide reductase A (MSRA: rs10903323 G/A) and vascular endothelial growth factor A (VEGFA: rs699947 C/A, rs2010963 G/C, and rs3025039 C/T) contribute to CAD susceptibility.Designs and methodsWe examined the association between the four polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS).ResultsWhen the MSRA rs10903323 GG homozygous genotype was used as the reference group, the GA and GA/AA genotypes were associated with a significantly increased risk of CAD (GA vs GG: adjusted OR = 1.36, 95% CI = 1.02–1.82, p = 0.038; GA/AA vs GG: adjusted OR = 1.33, 95% CI = 1.01–1.76, p = 0.042). The AA homozygous genotype was not associated with a risk of CAD. In the recessive model, when the MSRA rs10903323 GG/GA genotypes were used as the reference group, the AA homozygous genotype was not associated with a risk of CAD. Logistic regression analyses revealed that the VEGFA rs699947 C/A, VEGFA rs2010963 G/C, and VEGFA rs3025039 C/T polymorphisms were not associated with a risk of CAD.ConclusionsThese findings suggest that the functional MSRA rs10903323 G/A polymorphism is associated with CAD development. However, our results allow only a preliminary conclusion, which must be validated with a larger study of a more diverse ethnic population.     

The association between transforming growth factor β3 polymorphisms and left ventricular structure in hypertensive subjects

BackgroundTransforming growth factor β (TGF-β) may be a crucial regulator of cardiac remodeling. We investigated the association between the TGF-β gene polymorphisms and left ventricular structure.MethodsA total of 658 hypertensive subjects were genotyped for the TGF-β1 T869C and TGF-β3 (rs3917187 and rs4252338) polymorphisms.ResultsTGF-β3 rs3917187 AA homozygotes had, while accounting for covariates, greater left ventricular end-systolic (LVESD, P = 0.004) and end-diastolic dimension (LVEDD, P = 0.007) than G allele carriers. Moreover, left ventricular mass index (LVMI) in AA genotype was 123.0 ± 3.1 g/m² significantly higher than that in AG (114.6 ± 1.6 g/m²) and GG (115.4 ± 2.1 g/m², P = 0.03) genotypes. In multivariate regression analysis, TGF-β3 rs3917187 genotype as an independent predictor had statistically significant effects on LVESD (β = 0.164, P = 0.002), LVEDD (β = 0.172, P = 0.003) and LVMI (β = 0.136, P = 0.016), respectively. In further analyses, we observed a significant interaction between the rs3917187 and alcohol intake in relation to LVESD (P_int = 0.04) and left ventricular fractional shortening (LVFSH, P_int = 0.012). However, no relationship could be found between left ventricular parameters and the T869C or the rs4252338.ConclusionThe present results demonstrated that the TGF-β3 rs3917187 polymorphism was associated with left ventricular structure, and had an interactive influence with alcohol on LVESD and LVFSH in hypertensive subjects.     

The −351A/G polymorphism of ESR1 is associated with risk of myocardial infarction but not with extreme longevity

BackgroundWomen live longer than men. Some possible reasons for this advantage are the protection provided by high concentrations of 17β-estradiol (E2) during the premenopausal period and polymorphic variants of the estrogen receptors (ERs), which mediate various cardiovascular functions of E2.MethodsWe tested whether the ?351A/G and ?397T/C polymorphisms of the ERα-encoding ESR1 were associated with extreme longevity. The genomic DNA of 148 centenarians (C), 414 young controls (Y), and 208 myocardial infarction patients (MI) was analyzed by RFLP-PCR.ResultsBoth polymorphisms were equally distributed in the Y, C, and in centenarians never diagnosed with MI (HC). In centenarians, none of these polymorphisms was associated with a particular lipid profile. The AA genotype of the ?351A/G polymorphism was less frequent in the C, HC and Y groups than in MI patients (p = 0.058, p = 0.021, and p = 0.004, respectively). In MI patients, the GG genotype of the ?351A/G polymorphism was associated with significantly lower mean total cholesterol, LDL, and HDL levels compared to the AG (p = 0.0194, p = 0.0213, and p = 0.0367, respectively) and AA genotypes (p = 0.0014, p = 0.0078, and p = 0.0448, respectively).ConclusionsThe ?351A/G ESR1 polymorphism might be associated with MI, but not with extreme longevity.     

Receptor for advanced glycation end products (RAGE) and glyoxalase I gene polymorphisms in pathological pregnancy

ObjectivesThe aim of the study was to analyze polymorphisms of receptor for advanced glycation end products (RAGE) gene, and glyoxalase I gene and soluble RAGE, sRAGE, in physiological and pathological pregnancy.Design and methodsPolymorphisms of RAGE gene (? 429 T/C, ? 374 T/A, 557 G/A, 2184 A/G) and glyoxalase I gene (A419C) and sRAGE serum levels were determined in 284 women with pathological and physiological pregnancy.ResultsNo differences in distribution of genotype and allelic frequencies of studied polymorphisms were found. GA genotype of RAGE 557 G/A polymorphism (known as Gly82Ser) is associated with lower sRAGE serum levels in healthy pregnant women compared to GG genotype (483 ± 104 vs. 692 ± 262 pg/mL, p = 0.008). sRAGE correlates negatively with ALT in patients with pregnancy intrahepatic cholestasis (r = ? 0.536, p = 0.05).ConclusionsWe did not show any association of RAGE and glyoxalase I gene polymorphisms with pathological pregnancy, however further studies are needed to confirm the results.     

Clinical value of relative quantification ultrasound elastography in characterizing breast tumors

ObjectivesTo evaluate ultrasound elastography (USE) using strain ratio (SR), a relative quantification approach for breast lesions characterization.MethodsOne hundred forty-seven consecutive patients with a total of 156 breast lesions underwent USE. Technical accuracy was assessed automatically. For SR evaluation a rounded ROI was depicted inside fat (F), glandular tissue (G) and inside the lesion (L), preferably at the same depth. R1, mean value of the G and F ratio, stands for in background tissue composition elasticity. R2; mean value of L/F stands for in lesion elasticity, both evaluated in arbitrary unit (au). Two-years follow-up and pathology results were standard of reference. Mann–Whitney test, ROC analysis and Chi-square with Yates correction were used.ResultsWith the exception of 27 cysts, 17 malignant and 112 benign lesions were found. R1 values were 1.6 ± 0.7 au and 1.2 ± 0.9 au (p = 0.015 NS); R2 values were 6.1 ± 2.5 au and 1.9 ± 1.3 au (p < 0.001) for malignant and benign lesions, respectively. A threshold of 3.3 au showed a sensitivity and specificity of 88% and 87%, respectively with an AUC of 93%. Fifteen false positive and two false negative were detected.ConclusionRelative quantification of ultrasound elastography allows to find high levels of diagnostic accuracy in characterizing breast tumors above all in downgrading BI-RADS 3 and 4 lesions.     

Association of G-2548A LEP polymorphism with plasma leptin levels in Tunisian obese patients

ObjectivesThe aim of this study was to examine the association of the G-2548A polymorphism of the human leptin gene (LEP) with body mass index (BMI), plasma leptin, insulin, and lipid parameters in a sample of Tunisian population.Design and methodsTwo hundred and twenty nine obese patients (BMI ≥ 30 kg/m²) were screened and compared to 251 normal weight subjects (BMI < 25 kg/m²). The human leptin gene promoter G-2548A genotype was determined by polymerase chain reaction followed by a digestion with the restriction of endonuclease CfoI.ResultsIn the entire study sample, carriers of -2548A allele had significantly lower leptin levels than homozygous for -2548G allele (14.28 ± 9.10 ng/mL vs. 18.27 ± 12 ng/mL, p < 0.001 respectively) adjusted for BMI and gender. In obese patients but not control, subjects carrying the -2548A allele exhibited lower leptin levels than those with GG genotype (16.96 ± 8.27 ng/mL vs. 21.37 ± 11.72 ng/mL, p = 0.001 respectively) adjusted for BMI and gender. In this group, carriership of the -2548A allele was identified, by multiple linear regression models, as significant independent predictor for leptin levels variability. Separate analyses by gender revealed that only in obese women, the -2548A allele was found to be associated with lower leptin levels independently of BMI (p = 0.004).ConclusionsThe present study showed that G-2548A LEP polymorphism is associated with lower leptin levels in Tunisian obese women.     

MUC1 expression and its association with other aetiological factors and localization to mitochondria in preneoplastic and neoplastic gastric tissues

BackgroundThe molecular events that underlie the conversion of normal human gastric epithelium into adenocarcinoma are poorly understood. MUC1 overexpression and localization in mitochondria might confer cancer cells with attenuation of stress induced apoptosis. We studied MUC1 expression pattern, interaction with HSP70 and localization in mitochondria in preneoplastic and neoplastic human gastric tissues.MethodsImmunohistochemistry and Western blot were used to study MUC1 expression pattern and localization in mitochondria. Coimmunoprecipitation was used to study MUC1 interaction with HSP70. MUC1 expression was correlated with other causative features including erbB2 expression.ResultsMUC1 was expressed in 75.8% (147/194). MUC1 overexpression was detected in 50.0% (19/38 cases) dysplasia and 58.2% (32/55 cases) adenocarcinoma tissues. MUC1-CT–HSP70 interaction was seen in 71.66% (43/60 cases) and MUC1 localized to mitochondria in 33.33% (5/15) dysplasia samples and in 47.05% (8/17) adenocarcinoma samples. MUC1 expression showed significant association with smoking (χ² = 5.945; p < 0.015), alcohol consumption (χ² = 4.055; p < 0.044) and erbB2 positivity (χ² = 10.75; p < 0.001). MUC1 expression did not show appreciable association with age (χ² = 0.15; p < 0.698), sex (χ² = 0.22; p < 0.640) or Helicobacter pylori infection (χ² = 3.06; p < 0.080).ConclusionsSignificant correlation was found between MUC1 expression and smoking, alcohol and erbB2 expression. MUC1 showed aberrant expression in dysplasia and adenocarcinoma stages. MUC1 cytosolic tail was bound by HSP70 in all the stages but MUC1-CT was found to localize in mitochondria only in dysplasia and adenocarcinoma. MUC1-CT localization to mitochondria in dysplasia and adenocarcinoma might aid in the attenuation of epithelial stress response induced loss of polarity.     

Association of − 765G>C polymorphism of the COX-2 gene with recurrent embryo implantation failure in Southern Chilean women

BackgroundEmbryo implantation failure is considered an important cause of infertility in women undergoing assisted reproductive protocols. Recent studies demonstrated that the cyclooxygenase-2 (COX-2) enzyme is implicated in biosynthesis of prostaglandins and play an important role in the molecular implantation mechanisms. According to this evidence, we evaluated the potential association between the ? 765G>C (rs20417) polymorphism at the COX-2 gene and the implantation failure susceptibility in a sample of Chilean women.MethodsA total of 186 unrelated women matched by age were included in the present study, 106 patients (aged 31.9 ± 4.17 y) with no history of successful pregnancy and a diagnosis of infertility undergoing assisted reproductive protocols and 80 healthy controls (aged 31.4 ± 4.05 y). The COX-2 ? 765G>C gene polymorphism was analyzed by PCR-RFLP.ResultsGenotype distribution and allelic frequencies for ? 765G>C polymorphism of COX-2 gene were significantly different between patients and controls (P = 0.004 and P = 0.002, respectively). The odds ratio for implantation failure associated to the ? 765C allelic variant was 2.14 (95% C.I., 1.35–3.39, P = 0.00071).ConclusionOur data suggest, by the first time, that the COX-2 ? 765G>C polymorphism is associated with recurrent implantation failure in Chilean women and may constituted a novel molecular biomarker of reproductive failure.     

Programmed death-1 (PD-1) polymorphisms in Chinese patients with esophageal cancer

ObjectivesEsophageal cancer is an extremely aggressive gastrointestinal malignancy, which appears to result from a complex interplay between genetic and environmental agents. The genetic loci conferring susceptibility have yet to be fully defined. Considering the role of programmed death-1 (PD-1) in immune regulation and tumor pathogenesis, we genotyped three functional single nucleotide polymorphisms (SNPs) in PD-1 in a Chinese population to explore whether these three SNPs confer susceptibility to esophageal cancer.Design and methodsA total of 629 new diagnosed esophageal squamous cell carcinoma (ESCC) cases and 686 controls were recruited for this hospital-based case–control study. Genotyping was performed by the polymerase chain reaction–ligase detection reaction (PCR–LDR) method in all the subjects.ResultsIn the recessive model, when the PD-1 rs10204525 AA/AG genotypes were used as the reference group, the GG homozygote genotype was associated with a borderline statistically decreased risk of ESCC [adjusted odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.45–1.03, P = 0.067]. However, there were no significant associations between the other two SNPs and ESCC risk. Stratified analyses showed that a significantly decreased risk of ESCC associated with PD-1 rs10204525 A > G polymorphism was overt among male and younger patients.ConclusionsOur results demonstrate for the first time that the PD-1 rs10204525 polymorphism might contribute to susceptibility of ESCC and may therefore support the hypothesis that genetic variants, influencing T cell activity-associated gene regulation, may modify cancer risk.     

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.     

Nidogen-2: A new serum biomarker for ovarian cancer

Objectives:New ovarian cancer biomarkers suitable for early disease diagnosis, prognosis or monitoring could improve patient management and outcomes.Design and Methods:Nidogen-2 was measured by immunoassay in serum of 100 healthy women, 100 women with benign gynecological conditions and 100 women with ovarian carcinoma.Results:Serum nidogen-2 concentration between normal and benign disease patients was not different (median, 13.2 and 12.1 mg/L, respectively). However, nidogen-2 concentration in serum of ovarian cancer patients was elevated (median, 18.6 mg/L; p < 0.0001). Both nidogen-2 and CA125 were elevated more in serous histotypes of ovarian cancer and late state disease. Nidogen-2 and CA125 concentrations were strongly correlated. ROC curve analysis for nidogen-2 had an area under the curve (AUC) ranging from 0.73 to 0.83 but CA125 was superior (AUC ranging from 0.87 to 0.99). There was no complementarity between the two markers.Conclusions:Nidogen-2 is a new biomarker for ovarian cancer which correlates closely with CA125.     

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.     

Mutation -538 T/C in bone morphogenetic protein 4 do not increase the risk in sickle-cell disease with orthopedic complications but strongly associated with increased LDH and uric acid level in Indian patients from Chhattisgarh and Jharkhand states

BackgroundBone morphogenetic protein (BMP) are involved in the various orthopedic complications such as avascular necrosis, osteonecrosis and bone turnover, therefore genes coding for proteins, like BMP4, can be potential candidate for studying orthopedic disorders.MethodsA case–control study was conducted to examine the association between SNP T538C of BMP4 and orthopedic complications in sickling patients by employing PCR-RFLP.ResultsA total of 200 cases and 172 control groups were studied from Indian population. T538C SNP has not been implicated in disease and doesn't increase the risk (OR = 0.89, OR = 0.68). We observed no significant association between the T538C polymorphism and case group in the studied population. However, we observed significantly increased uric acid and LDH level in homowild (TT), heteromutant (TC) and homomutant (CC) in case group compared to control group ( all p = 0.0001) and (p = 0.0001, p = 0.0001, p = 0.015 and p = 0.0001, p = 0.0001, p = 0.0001 respectively) in the studied population.ConclusionsThe T/C polymorphism in BMP4 is not associated with case group and in view of present observation, we suggest that evaluation of LDH and uric acid level and its association with polymorphisms in the BMP4 may be considered to be reliable molecular and biochemical markers, and possess promising rational for diagnostic potential in clinical cases.     

Effect of a high-intensity interval training on serum microRNA levels in women with breast cancer undergoing hormone therapy. A single-blind randomized trial

BackgroundThe role of microRNAs (miRs) in hormone therapy (HT) is of keen interest in developing biomarkers and treatments for individuals with breast cancer. Although miRs are often moderate regulators under homeostatic conditions, their function is changed more in response to physical activity.ObjectiveThis single-blind randomized trial aimed to explore the effect of high-intensity interval training (HIIT) on serum levels of miRs in individuals with early-stage breast cancer undergoing HT.MethodsHormone receptor-positive women with breast cancer and healthy women were randomly assigned to a healthy control group (n = 15), healthy group with HIIT (n = 15), breast cancer group with HT (HT, n = 26), and breast cancer group with HT and HIIT (HT + HIIT, n = 26). The exercise groups underwent interval uphill walking training on a treadmill 3 times a week for 12 weeks. At the end of the study, we analyzed changes in levels of cancer-related miRs (oncomiRs) and tumour suppressor miRs (TSmiRs) in response to the HT and HIIT.ResultsIn women with breast cancer versus healthy controls, the expression of some oncomiRs was significantly increased — miR-21 (P < 0.001), miR-155 (P = 0.001), miR-221 (P = 0.008), miR-27a (P < 0.001), and miR-10b (P = 0.007) — and that of some TSmiRs was significantly decreased — miR-206 (P = 0.048), miR-145 (P = 0.011), miR-143 (P = 0.008), miR-9 (P = 0.020), and let-7a (P = 0.005). Moreover, HT considerably downregulated oncomiRs and upregulated TSmiRs. HIIT for 12 weeks with HT significantly decreased the expression of the oncomiRs and significantly increased that of the TSmiRs as compared with HT alone.ConclusionsHITT could amplify the decrease and/or increase in expression of miRs associated with HT in women with breast cancer. A prospective trial could determine whether the use of circulating miRs for monitoring treatment can be useful in therapy decisions.Trial registrationIranian Registry of Clinical Trials (No.: IRCT201202289171N1).     

Interethnic differences in ADMA concentrations and negative association with nitric oxide formation in preeclampsia

BackgroundRecent studies have suggested that impaired nitric oxide (NO) formation in preeclampsia may result from increased concentrations of an endogenous NO synthase inhibitor, the asymmetric dimethylarginine (ADMA). However, no previous study has examined whether a negative association exists between ADMA and nitrite concentrations in preeclampsia. Moreover, no previous study has compared ADMA and nitrite levels in black and white preeclamptic pregnant women.MethodsWe measured plasma nitrite concentrations using an ozone-based chemiluminescence assay, and plasma ADMA levels using enzyme immunoassays in 94 pregnant (47 healthy pregnant: 16 blacks and 31 whites; and 47 preeclamptic: 14 blacks and 33 whites).ResultsWe found higher ADMA (2.199 ± 0.016 μmol/l vs. 2.112 ± 0.012 μmol/l; P < 0.0001) and lower plasma nitrite levels (102 ± 7.1 nmol/l vs. 214.8 ± 26.1 nmol/l; P < 0.0001) in preeclamptic compared with healthy pregnant women. Black pregnant had higher ADMA levels than white pregnant women (P < 0.05), both in preeclamptic (2.239 ± 0.020 μmol/l vs. 2.144 ± 0.019 μmol/l) and in healthy pregnant (2.172 ± 0.025 μmol/l vs. 2.077 ± 0.018 μmol/l). Conversely, we found no significant effects of ethnicity on the plasma nitrite levels, both in healthy pregnant and in preeclamptic women (P > 0.05). We found a significant negative correlation (P < 0.05) between these markers (r = ? 0.28; P < 0.05).ConclusionsOur findings show higher ADMA and lower nitrite levels in preeclamptic compared with healthy pregnant, and the concentrations of these biomarkers are inversely associated. While ethnicity affected ADMA concentrations, no such effect was found with respect to nitrite levels. These results may have important implications for studies on NO biology and therapeutic approaches of preeclampsia.     

The functional Toll-like receptor 4 Asp299Gly polymorphism is associated with lower left ventricular mass in hypertensive women

BackgroundThis study investigated the impact of a putative functional TLR4 polymorphism (Asp299Gly) on left ventricular (LV) structure in hypertensive subjects.MethodsA sample of 443 patients (266 women and 177 men) was evaluated by clinical history, physical examination, anthropometry, analysis of inflammatory and metabolic parameters, echocardiography and TLR4 Asp299Gly genotyping. In addition, the relationship between the polymorphism and in vitro lipopolysaccharide responsiveness of peripheral blood monocytic cells was also assessed.ResultsWomen carrying the 299Gly allele presented lower posterior wall thickness (p = 0.01), interventricular septum thickness (p = 0.04), LV mass (p = 0.01) and LV mass index (p = 0.03), as well as a reduced prevalence of LV hypertrophy (p = 0.002), in comparison to women with the wild-type genotype. These results were confirmed by stepwise and logistic regression analyses adjusted for potential confounders. Conversely, the 299Gly allele did not influence LV structure in men. Furthermore, in vitro assays revealed that monocytes of either men or women heterozygous for the 299Gly allele presented a lower lipopolysaccharide-induced production of interleukin-6, compared to non-carriers.ConclusionsThe functional TLR4 Asp299Gly polymorphism is associated with lower LV mass in hypertensive women. These findings suggest that interactions among gender, LV remodeling and TLR4 gene variants may occur in hypertensive subjects.