Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease

ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.     

Functional vascular endothelial growth factor gene polymorphisms and diabetes: Effect on coronary collaterals in patients with significant coronary artery disease

BackgroundVascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. This study tested the association between functional VEGF + 405 C > G (rs2010963), ? 2578C > A (rs699947) polymorphisms, and coronary collaterals in patients with coronary artery disease (CAD).MethodThe collateral scoring system developed by Rentrop was used to classify 393 patients according to their collaterals as either “poor” (grades 0 and 1) or “good” (grades 2 and 3). Gene polymorphisms were analyzed by TaqMan assay.ResultsThe frequency of + 405C and ? 2578A alleles was higher in the good collaterals group (p = 0.007 and 0.005, respectively). For the + 405C > G allele, the odds ratio (OR) of good collaterals for CC to GG genotype was 2.54 (p = 0.003). For the ? 2578A allele, the OR of good collaterals for AA to CC genotype was 2.31 (p = 0.038). Univariate and logistic regression analysis found 2 polymorphisms in the additive model for associations with collateral development: + 405C > G (p = 0.005 and 0.010) and ? 2578C > A (p = 0.006 and 0.006). The VEGF + 405C > G polymorphism and DM revealed an interactive effect on collateral development (p = 0.027).ConclusionsThe VEGF + 405C > G and ? 2578C > A polymorphisms might be novel genetic factors affecting collateral development in Chinese patients.     

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.     

A polymorphism in the resistin gene promoter is related to increased C-reactive protein levels in patients with coronary artery disease.

BACKGROUND: Resistin, a novel adipocyte-derived peptide, has been linked to inflammatory process and coronary artery disease (CAD). The -420C>G polymorphism located in the resistin gene (RETN) promoter has recently been suggested to play a potential role in proinflammatory conditions (e.g., atherogenesis). However, whether this polymorphism has any effect on the inflammatory process in patients with stable CAD is unclear. METHODS: The RETN -420C>G polymorphism was determined by using PCR-restriction fragment length polymorphism. Plasma lipid profiles, glucose and high-sensitivity C-reactive protein (hs-CRP) were measured in fasting state. RESULTS: Patients with variant genotypes (CG+GG) had significantly higher levels of hs-CRP than CC carriers (adjusted p<0.001). In addition, the variant genotypes were observed to be independently associated with higher hs-CRP levels (>3 mg/L, p=0.004). However, no association was found between this polymorphism and plasma lipids or glucose levels. CONCLUSION: Our data suggest that the RETN -420C-to-G variant is associated with increased CRP levels in patients with stable CAD, suggesting that the RETN -420C>G polymorphism may be potentially involved in the inflammatory component of atherogenesis through an enhanced production of CRP.     

ChREBP gene polymorphisms are associated with coronary artery disease in Han population of Hubei province

BackgroudChREBP regulates lipogenesis and glucose utilization in the liver. Current reports suggest a contradictive association between rs3812316 of this gene and triglyceride level. We hypothesized the polymorphisms in ChREBP gene were associated with CAD in Chinese population.MethodsThe ChREBP gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 200 controls and 310 CAD patients. Serum lipids and glucose concentrations were measured in all subjects. Haplotypes were constructed based on rs3812316, rs7798357 and rs1051921. All the data were analyzed using SPSS14.0, PLINK1.07 and SHEsis software.ResultsThe rare allele G of rs3812316 was significantly lower in the CAD group after adjusting for age, sex, BMI, SBP and DBP (OR^a = 0.589, 95%CI = 0.361–0.961, P = 0.034). No significant differences between cases and controls were found in genotype or allele distributions of rs7798357, rs17145750 and rs1051921. Haplotype CGC was significant higher in CAD group (P < 0.01, OR = 2.364, 95%CI = 1.608–3.474), while haplotypes GGC, CGT, CCC were significant lower in CAD group (P < 0.05).ConclusionsThe rs3812316 and the haplotypes in ChREBP gene appeared to be related to high susceptibility to CAD.     

Estimated glomerular filtration rate for drug dose adjustment: Cockcroft and Gault or abbreviated MDRD equation?

ObjectivesEvaluate if Cockcroft and Gault (CG) estimated glomerular filtration rate (eGFR) might be replaced by abbreviated MDRD eGFR for drug dose adjustment.Design and methodseGFR was determined in 140 hospitalized patients (median: 68 years, 65 kg) treated by nephrotoxic and/or renally cleared drugs.ResultsCG eGFR was 61 mL/min vs. 78 mL/min/1.73 m² for MDRD (p < 0.0001). CG-MDRD difference ranged from ? 93 to + 34 mL/min, influenced by patient age, weight, and gender (p < 0.001).ConclusionsCG eGFR cannot be easily replaced by abbreviated MDRD eGFR for drug dose adjustment.     

Simultaneous detection of CYP3A5 and MDR1 polymorphisms based on the SNaPshot assay

BackgroundThe 6986A> G polymorphism for CYP3A5 and the ?129T> C, 1236C> T, 2677G> T/A, and 3435C> T polymorphisms for MDR1 are considered the major genetic factors affecting a range of drugs' metabolism and transport. Simultaneous genotyping of these five polymorphisms would be useful for estimating the therapeutic effects of their related drugs.Subjects and methodsWe have described a SNaPshot assay that can simultaneously detect all the five polymorphisms based on multiplex PCR and minisequencing reaction. A total of 168 unrelated Chinese DNA samples were used to establish and evaluate the assay.ResultsThe different genotypes of the five polymorphisms could be determined by peak retention time and colors. DNA sequencing was performed on samples randomly selected from each of the genotype groups detected by SNaPshot assay, and the results indicated 100% concordance.ConclusionThe SNaPshot assay for the CYP3A5 and MDR1 five polymorphisms detection was accurate, automated, and cost-effective.     

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.     

Genetic variant in visfatin gene promoter is associated with decreased risk of coronary artery disease in a Chinese population

BackgroundVisfatin is a newly identified pro-inflammatory adipokine expressed predominantly in visceral fat. Previous studies have suggested a role for visfatin in low-grade inflammation and regulation of lipid metabolism. Most recently, a genetic polymorphism ? 1535C > T located in the visfatin gene promoter has been identified, and suggested to be associated with the regulation of visfatin expression, lipid levels. However, it is unclear whether this polymorphism has a linkage with CAD.MethodsWe conducted a hospital-based case-control study with 257 CAD patients and 292 controls to examine the potential association of the Visfatin ? 1535C > T polymorphism with CAD.ResultsThe frequencies of the CC, CT, and TT genotypes in cases were significantly different from those of controls (χ² = 6.223, P = 0.045). Subjects with the variant genotypes (CT + TT) had a 40% decreased risk of CAD relative to CC carriers (adjusted OR = 0.60, 95%CI = 0.40–0.89). Furthermore, the adjusted OR of a TT genotype for CAD was 0.52 (95%CI = 0.31–0.87). There was a significant association between Visfatin ? 1535C > T polymorphism and triglyceride levels in both CAD patients and controls (P = 0.003, 0.018, respectively). In stratified analyses, the T allele was significantly associated with reduced risk of CAD in males, subjects with age < 59 years, and non-smokers. Moreover, a borderline statistical significance (P = 0.058 for trend) was observed between the variant genotypes and severity of CAD.ConclusionOur results suggested that Visfatin ? 1535C > T polymorphism might be associated with reduced risk of CAD in a Chinese population.     

Monocyte chemoattractant protein 1-2518 A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population

BackgroundHyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese.MethodsWe conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls.ResultsCompared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR = 0.49, 95% CI 0.32–0.77, P < 0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤ 50) (adjusted OR = 0.35, 95% CI 0.20–0.61, P < 0.0001), and similar results were observed in males (adjusted OR = 0.37, 95% CI 0.21–0.66, P = 0.001) and urban participants (adjusted OR = 0.35, 95% CI 0.21–0.58, P < 0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio.ConclusionsOur present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population.     

Are preservatives necessary in 24-hour urine measurements?

Background24-h urine measurements are used in the routine diagnosis and follow-up of many diseases in the clinical laboratory. Calcium (Ca²⁺), magnesium (Mg²⁺), phosphate (PO₄^3?) and uric acid are frequently requested markers in 24-h urine samples. Because of the different solubilities of these parameters, different urine collection conditions – urine in base for uric acid and urine in acid for Ca²⁺, PO₄^3? and Mg²⁺ measurements – are recommended.MethodsWe aimed to test the effect of addition of preservatives and heating of the urine specimen on the results obtained for Ca²⁺, Mg²⁺, PO₄^3? and uric acid by comparison with untreated samples results. Spot (n = 20) and 24-h urine (n = 50) samples were obtained from patients for routine urine analysis. A single spot urine sample was divided into five aliquots of 10 mL each: one containing 200 µL of HCl (6 N), another containing 200 µL of sodium bicarbonate, NaHCO₃ (5 g/L), two others in which the same preservative agents were added 24 h after the collection, and one without any preservative (untreated). Ca²⁺, PO₄^3?, uric acid and Mg²⁺ were measured in triplicate and at three different time points during the study: at the time of sampling (0 h), 24 h after sampling, and after heating the samples. The 24-h urine samples were collected without preservatives and analytes were measured promptly before and after acidification/alkalinization.ResultsThere was no statistically significant difference between untreated and treated samples (p > 0.05). Heating also failed to show any difference in the results (p > 0.05).ConclusionAccording to our results, addition of preservatives is not necessary for measurement of Ca²⁺, Mg²⁺, PO₄^3? and uric acid in promptly assayed 24-h urine samples.     

Plasminogen activator inhibitor-1 5G/5G genotype is a protecting factor preventing posttransplant diabetes mellitus

ObjectivePlasminogen activator inhibitor 1 (PAI-1) is thought to play a role in the pathogenesis of obesity and insulin resistance. A connection between gestational diabetes mellitus and the functional -675 PAI-1 genotype has been reported. Therefore, we examined the role of the PAI-1 gene polymorphism in kidney transplant recipients.MethodsA total of 376 kidney transplant recipients were prospectively screened for posttransplant diabetes mellitus (PTDM). Eighty-one (21.5%) patients were diagnosed with PTDM and the other 295 patients were non-diabetic following kidney transplantation. DNA samples were isolated from the sera and analyzed for the functional ? 675 4G/5G promoter polymorphisms of the PAI-1 gene.ResultsKidney transplant recipients with PTDM were significantly associated with tacrolimus use (p = 0.03), older age (p = 0.036), and higher body mass index (p = 0.001). The genotype distribution was significantly different between the patients with PTDM (genotype 4G/4G:4G/5G:5G/5G = 33.3%:60.5%:6.2%) and those without PTDM (genotype 4G/4G:4G/5G:5G/5G = 36.9%:44.1%:19.0%) (p = 0.018). Patients with homozygosity for 5G had a significantly lower rate of PTDM (aOR, 0.286, p = 0.022) and higher cumulative event-free probability of time to PTDM (log rank test, p = 0.0058).ConclusionHomozygosity for the 5G allele of the PAI-1 gene constitutes a protecting factor for the development of PTDM. Our findings are similar to a previous study on gestational diabetes mellitus, and strongly support a possible genetic role of PAI-1 in the development of PTDM.     

The association of ghrelin polymorphisms with coronary artery disease and ischemic chronic heart failure in an elderly Chinese population

ObjectiveTo investigate the association of coronary artery disease (CAD) and ischemic heart failure (IHF) with polymorphisms of the ghrelin gene in elderly Chinese patients.Design and methodsFifty-six patients with ischemic heart failure, sixty patients with coronary artery disease without heart failure, and one hundred healthy control subjects participated in the study. The polymorphisms were evaluated by polymerase chain reaction, sequencing, and fragment length polymorphism analysis.ResultsOnly one single nucleotide polymorphism (SNP), Leu72Met (408C/A), was observed across all samples. Gene frequencies of CC and allele frequencies of C were significantly greater in the CAD with IHF group than those in the CAD without IHF group (p = 0.025, p = 0.011). There was no significant association between the Leu72Met SNP with coronary artery disease risk factors.ConclusionOur results suggest that a C allele at position 408 of the ghrelin gene is associated with genetic susceptibility to ischemic heart failure in Chinese elders.     

The association of myeloperoxidase promoter polymorphism with carotid atherosclerosis is abolished in patients with type 2 diabetes

ObjectivesType 2 diabetes mellitus (DM) enhances the development of atherosclerosis and reduces the activity of the oxidative myeloperoxidase (MPO) enzyme. MPO gene has a functional promoter polymorphism ?463G/A which leads to high- (GG) and low-expression (AG, AA) genotypes.Design and methodsWe studied the association of MPO polymorphism with carotid artery intima-media thickness (IMT) in 198 randomly selected Finnish men of Caucasian origin, 161 non-diabetics and 37 with type 2 DM. Their carotid IMT was measured by high-resolution ultrasonography, and the overall mean IMT value was calculated. MPO genotypes were determined by the PCR-RFLP method.ResultsWe found significant MPO genotype-by-study-group (control/DM) interactions with the overall mean IMT and internal carotid IMT (p = 0.05 and p = 0.04, respectively). Among non-diabetic subjects, the overall carotid IMT was 7.3% higher in subjects with the low-activity genotype when compared to the high-activity (G/G) group. The results remained significant after adjustment for total cholesterol and smoking (p = 0.015). No similar genotypic association was found for the subjects with type 2 DM.ConclusionsThis data suggests that in subjects with normal glucose metabolism, MPO gene variation may modify the carotid artery IMT.     

TNF-α −308G > A and IL-6 −174G > C polymorphisms in Tunisian patients with coronary artery disease

ObjectiveOur aim was to evaluate the contribution of tumor necrosis factor (TNF)-α ?308G > A and interleukin (IL)-6 ?174G > C gene promoter variants to the presence of coronary artery disease (CAD) in Tunisians.Design and methodsStudy subjects comprised 418 angiographically proven CAD patients and 406 age-, gender-, and ethnic origin-matched controls. Genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.ResultsThere were no significant differences in the allelic distribution of TNF-α ?308A (19.6% vs. 19.0%, P = 0.73), and IL-6 ?174C (15.6% vs. 14.3%, P = 0.47) promoter polymorphisms between CAD patients and control subjects, respectively. In addition, single locus analysis revealed no differences in genotype frequencies between the two study groups, and the combined distribution of both genotypes did not differ significantly between controls and CAD patients (P > 0.05).ConclusionThere is no allelic or genotypic association of TNF-α ?308G > A and IL-6 ?174G > C promoter polymorphisms with CAD in Tunisians, thereby confirming an ethnic-selective contribution of both gene variants to CAD presence.     

An oxidative stress score as a combined measure of the pro-oxidant and anti-oxidant counterparts in patients with coronary artery disease

Oxidative stress plays a key role in the pathogenesis and development of atherosclerosis.AimTo evaluate the relationship between a novel oxidative stress index (reflecting both oxidative and anti-oxidant counterparts) with traditional cardiovascular risk factors and C-reactive protein (CRP) in coronary artery disease (CAD).Methods100 angiographically proven CAD and 70 control subjects (mean age: 65 ± 10 years, 110 males), underwent a global cardiovascular risk assessment and serum CRP and oxidative stress estimation. The Oxidative-INDEX was calculated after automated evaluation of serum hydroperoxides and total anti-oxidant capacity (D-ROM and OXY-adsorbent Test, Diacron, Italy) subtracting the OXY standardized variable from the ROM standardized variable.ResultsThe Oxidative-INDEX was higher in CAD with respect to control subjects (p < 0.001). A stepwise elevation in the Oxidative-INDEX levels was found depending on the number of affected vessels (p < 0.001). Oxidative stress was elevated according to the presence of diabetes (p < 0.001), smoking habit (p < 0.01), and hypercholesterolemia (p < 0.05). Oxidative-INDEX significantly correlated with aging (p ≤ 0.05) and CRP (p < 0.001). The Oxidative-INDEX increased with the number of cardiovascular risk factors (p < 0.001).After adjustment for traditional CV risk factors, the multivariate logistic regression analysis indicated the Oxidative-INDEX concentration as an independent factor for CAD (odds ratio = 1.4, confidence intervals = 1.1–1.9, p < 0.05).ConclusionOxidative stress represents a shared molecular pathway in atherosclerotic-related conditions, and its estimation by the automated Oxidative-INDEX could represent a valuable tool and a promising target in the prevention, diagnosis and treatment of CAD in the clinical setting.     

Association of the TNF-α -308G/A polymorphism with family history of type 2 diabetes mellitus in a Mexican population

AimsWe examined the possible association of the ? 308G/A polymorphism of the TNF-α promoter gene in type 2 diabetes mellitus (DM2) patients and in non-diabetic subjects with and without family history of DM2.MethodsWe studied 87 non-diabetic subjects without DM2 family history in at least one of two generations, 48 non-diabetic subjects with DM2 family history and 95 DM2 patients. Genotyping was carried out by PCR-RFLP.ResultsThe frequency of TNF-α ? 308G/A genotype was significantly lower in non-diabetic subjects without DM2 relatives (6%) as compared to DM2 patients (24%) (odds ratio (OR) = 5.24; 95% confidence interval (CI) = 1.9–15.8, p < 0.0005), but similar to non-diabetic subjects with DM2 relatives (29%) (OR = 0.77; CI = 0.3–1.7, p = 0.4). Logistic regression analysis showed the association of TNF-α ? 308G/A polymorphism with DM2 family history (OR = 5.80; CI = 1.77–18.98, p < 0.0003).ConclusionsOur results suggest that TNF-α ? 308G/A polymorphism is associated with DM2 family history and is a risk factor for DM2.     

Increased clopidogrel response is associated with ABCC3 expression: a pilot study

BackgroundThe aim of this study was investigate the relationship between ABCB1 and ABCC3 gene expressions in peripheral blood cells (PBC) and the response to clopidogrel in patients with coronary arterial disease (CAD).MethodsTwenty-six male CAD patients (50–70 years) under treatment with clopidogrel (75 mg/day) for at least 5 days were selected. Blood samples were obtained to evaluate platelet reactivity and ABCB1 and ABCC3 mRNA expression. Platelet reactivity was measured in P2Y12 Reaction Units (PRU) using VerifyNow. RNA was extracted from PBC and mRNA levels were measured by qPCR, using GAPD as a reference gene.ResultsPlatelet response to clopidogrel was categorized in to PRU quartiles. Individuals with PRU values within the first quartile (Q1, < 151 units) were considered good responders, while those who had PRU within the fourth quartile (Q4, PRU > 260) were considered non-responders. ABCC3 was 1.7 times more expressed in Q4 than in Q1 PRU group (p = 0.048). Moreover, CAD patients with low ABCC3 expression (Qe1, < 2.5 × 10^? 3) had higher probability to have a good response to clopidogrel (OR: 18.00, 95%CI: 1.90–169.99, p = 0.001). Univariate linear regression analysis demonstrated that low ABCC3 mRNA expression contributed with a reduction of 73 PRU in relation to the patients with expression value higher than 2.5 × 10^? 3 (p = 0.027). Neither ABCB1 mRNA levels nor clinical variables studied influenced PRU values.ConclusionsLow ABCC3 mRNA expression in peripheral blood cells is associated with increased clopidogrel response, but further studies are needed to describe the functional relationship of clopidogrel with the ABCC3.     

Genetic risk factors for renal failure among north Indian ESRD patients

ObjectivesAngiotensin converting enzyme (ACE), G-Protein couple receptor (G-Prot), endothelial nitric oxide synthase (ecNOS), Leptin ? 2548G/A and uncoupling protein (UCP2) are potent regulators of intra renal hemodynamics and may be the causative factors contributing to the deterioration of renal functions. In recent years few studies have been published to show the association of these markers with the end stage renal disease (ESRD). Our study was designed to see the role of different genetic factors individually and synergistically in the progression of renal failure.Design and methodsThe genotypes of these markers were determined by PCR and RFLP. The gene frequencies of ACE, G-protein, ecNOS, Leptin and UCP2 in 184 ESRD patients and 569 healthy controls from North India were compared.ResultsThere was a significant difference between ESRD patients and control groups both in the biochemical parameters and genotype frequencies. The genotype distribution of ACE in patients was significantly different from the controls (p = 0.0001; OR = 9.428; 95% CI = 4.56–19.492). There was no difference observed for the GNB3-825 TT genotype and for ecNOS aa genotype in patient and control groups. The distribution of Leptin ? 2548G/A genotype and UCP2 genotype in patients were significantly different from that of controls (p = 0.0013; OR = 2.804; 95% CI = 1.501–5.237 and p = 0.0001; OR = 8.853; 95% CI = 3.458–22.667 respectively).ConclusionsOur results propose that the ACE-DD, Leptin AA and UCP2-DD genotype may be potential genetic markers for predicting the causation and progression of chronic renal failures.     

A cross-sectional study of the association between heat shock protein 27 antibody titers, pro-oxidant-antioxidant balance and metabolic syndrome in patients with angiographically-defined coronary artery disease

ObjectiveTo investigate the association between serum antibody titers to Hsp27 (anti-Hsp27) and pro-oxidant–antioxidant balance (PAB) in patients with angiographically-defined coronary artery disease (CAD) with or without the metabolic syndrome (MS).DesignSubjects (n = 243) were classified into MS+ (n = 161) and MS? (n = 82) subgroups, based on the AHA/NHBLI criteria.ResultsSerum anti-Hsp27 titers were found to be significantly higher in the MS+ vs. MS? group. However, no significant difference was observed in serum PAB values. When assessed for individual components of MS, increased serum anti-Hsp27 was found to be higher in subgroups with elevated triglycerides, elevated blood pressure and reduced high-density lipoprotein cholesterol (HDL-C). Subgroups of patients with elevated triglycerides had higher PAB values. HDL-C was the only significant predictor of anti-Hsp27 in the population as a whole.ConclusionThe evidence from this investigation indicates the presence of elevated anti-Hsp27 in patients with concurrent CAD and MS compared to those with CAD alone.