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.     

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.     

Heritability of genetic variants of resistin gene in patients with coronary artery disease: a family-based study

ObjectiveThe resistin gene (RETN) ?420 C > G and + 299 G > A polymorphism was investigated in a case-control study from forty complex Pakistani families with coronary artery disease (CAD) history. Heritability of the susceptible/variant alleles was investigated from parent–offspring trios in these families.MethodResistin levels were determined from 239 individuals by enzyme-linked immunosorbent assay. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism.ResultsElevated resistin levels were observed from CAD cases vs. controls (p < 0.0001). The RETN ? 420 C > G and + 299 G > A polymorphism was more prevalent in cases vs. controls (p < 0.0001). The transmission disequilibrium test revealed a significant association of the ? 420 and + 299 polymorphism with CAD (χ² = 34.4, p < 0.0001 and χ² = 31.6, p < 0.0001, respectively).ConclusionElevated resistin, and the RETN ?420 C > G and + 299 G > A polymorphism may contribute to familial CAD. The ? 420 and + 299 variant alleles are transmitted more frequently from parent to affected offspring. This is the first report on the association of the RETN + 299 G > A polymorphism with CAD.     

Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

ObjectivesMatrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population.Design and methodsStudy enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms ? 1607 1G/2G, ? 519 A/G and ? 340 T/C were genotyped by PCR and RFLP methods.ResultsIndividuals carrying MMP-1 ? 1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR = 1; OR = 1.87 95% CI 1.29–2.07; OR = 3.49 95% CI 1.67–7.30, p = 0.0009, respectively). Compared to the referent haplotype 2G_? 1607-T_? 340-A_? 519, the haplotypes 1G_? 1607-T_? 340-A_? 519, 1G_? 1607-T_? 340-G_? 519 and 2G_? 1607-C_? 340-A_? 519 had statistically significant protective effect on CP presence (OR = 0.41, 95% CI 0.29–0.81, p = 0.01; OR = 0.56, 95% CI 0.44–0.89, p = 0.01; OR = 0.43, 95% CI 0.27–0.86, p = 0.02, respectively).ConclusionsMMP-1 ? 1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.     

Association of exonic variants of Klotho with metabolic syndrome in Asian Indians

BackgroundKlotho, an anti-aging gene, is a functional candidate for metabolic syndrome. We conducted a cross-sectional study to evaluate the association of the genetic variants of Klotho with metabolic syndrome and surrogates of insulin resistance in Asian Indians.MethodsWe recruited 428 clinically normal subjects for the study. Genotyping was done by polymerase chain reaction and restriction fragment length polymorphism.ResultsSignificant and borderline associations of the KL-VS (OR = 15.88 [95%CI, 2.56–98.70], p = 0.003) and C1818T (OR = 0.28 [95%CI, 0.07–1.07], p = 0.063) variants of the Klotho gene, respectively, were observed with metabolic syndrome. The association of the KL-VS variant with metabolic syndrome could be linked to its observed influence on high blood glucose (OR = 6.92 [95% CI = 1.75–27.44], p = 0.006), high blood pressure (OR = 5.21 [95%CI = 1.00–38.43], p = 0.046), insulin resistance (OR = 3.59, [95%CI = 1.01–12.79], p = 0.048) and trend towards its association with hypertriglyceridemia (OR = 3.69 [95%CI = 0.92–14.77], p = 0.065).ConclusionsThe genetic variants of Klotho might predict risk for metabolic syndrome and insulin resistance in Asian Indians. However, larger studies in other ethnic populations are warranted to determine the role of these gene variants in the etiology of metabolic syndrome.     

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.     

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.     

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.     

Investigation of the effect of donor platelet endothelial cell adhesion molecule 1 polymorphism on the graft-vs.-host disease occurrence in Tunisian recipients of hematopoietic stem cells

ObjectiveThe aim of this study is to examine the effect of donor PECAM-1 alleles and haplotypes for the SNPs L98V, S536N, and R643G on the occurrence of GVHD in Tunisian recipients of HSCs.Design and methodsThis study enrolled 102 patients and their 102 respective HLA-identical sibling donors of HSCs. The PECAM-1 SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR).ResultsThe single marker association analysis showed that the L98 allele, in a recessive genetic model, may be a potential risk factor only for acute GVHD (p = 0.036, OR = 2.580, 95% C.I. = 1.053–6.326). However, the haplotype analysis showed a lack of association between donor's PECAM-1 SNPs and GVHD incidence in recipient.ConclusionThe homozygosity state for donor PECAM-1 L98 allele may be a significant risk factor for acute GVHD. This is probably due to its action on the function of donor leukocytes especially during the extravasation process.     

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.     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.     

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.     

Association of MMP-3 5A/6A gene polymorphism with susceptibility to carotid atherosclerosis

ObjectivesStromelysin-1 (MMP-3) as a key member of metalloproteinase family could have an important role in atherogenesis. The 5A/6A polymorphism in the promoter of MMP-3 gene affects the level of MMP-3 gene expression. We assessed whether the MMP-3 promoter low- and high-activity genotypes are related to susceptibility for carotid atherosclerosis (CA) in Serbian population.Design and methodsThe study group of case-control design consisted of 515 participants. The 265 patients with ultrasonographic evidence of carotid plaque presence were recruited for the study. The 5A/6A polymorphism was typed by RFLP-PCR.ResultsThere was significantly higher prevalence of genotypes containing 6A allele in the patients with CA compared to controls (p < 0.05). The model of inheritance with the dominant effect of 6A allele gave elevated and significant OR for carotid atherosclerosis (adjusted OR 2.35, CI = 1.0–5.5, p = 0.048).ConclusionsSubjects carrying genotypes with 6A allele had significantly higher susceptibility to carotid atherosclerosis.     

Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia

BackgroundStatins are normally the first-line therapy for hypercholesterolemia (HC); however, the lipid-lowering response shows high interindividual variation. We investigated the effect of four polymorphisms in CYP3A4, CYP3A5 and ABCB1 genes on response to atorvastatin and CYP3A4 activity in Chilean subjects with HC.MethodsA total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipid levels before and after treatment were measured. Genetic variants in CYP3A4 (? 290A>G, rs2740574), CYP3A5 (6986A>G, rs776746) and ABCB1 (2677G>A/T, rs2032582 and 3435C>T, rs1045642) were analyzed by PCR-RFLP. CYP3A4 enzyme activity in urine samples was assessed through determination of 6β-hydroxycortisol/cortisol free ratio (6βOHC/FC).ResultsAfter 4 weeks of therapy, a significant reduction in total cholesterol (TC) and LDL-c was observed (P < 0.001). The G allele for ? 290A>G polymorphism was related to higher percentage of variation in TC and LDL-c (P < 0.001). Moreover, same allele was associated with higher HDL-c variation (P = 0.017). In addition, CYP3A4 enzyme activity was lower in subjects carrying this polymorphism (P = 0.009). No differences were observed for CYP3A5 and ABCB1 variants.ConclusionOur results suggest that presence of G allele for ? 290A>G polymorphism determines a better response to atorvastatin, being also associated with lower CYP3A4 activity in vivo, causing an increased atorvastatin activity.     

Associations between genetic polymorphisms of paraoxonase genes and coronary artery disease in a Taiwanese population

ObjectiveWe evaluated the relationship between polymorphisms of the paraoxonase (PON) gene and the risk of coronary artery disease (CAD) in Taiwanese patients.MethodsOur sample set included 369 volunteers, classified into two groups: 162 healthy volunteers and 207 CAD patients aged 60.0 ± 9.7 and 64.3 ± 12.3 years, respectively. Polymorphisms of the PON1 and PON2 genes were determined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) techniques.ResultsThe results indicate that for the PON1 gene, the homozygous genotype RR was found significantly more often among the CAD group compared with the healthy group (OR = 1.965, 95% CI = 1.223–3.159, p = 0.005). Furthermore, for the PON2 gene, the homozygous genotype CC was found significantly more often among the CAD group compared with the control group (OR = 2.525, 95% CI = 1.103–5.780, p = 0.026).ConclusionsIndividuals homozygous for the R allele of the PON1 gene and the C allele of the PON2 gene are more likely to have an increased risk of CAD.     

Gingival crevicular fluid PGE2, IL-1beta, t-PA, PAI-2 levels in type 2 diabetes and relationship with periodontal disease

ObjectivesTo evaluate if type 2 diabetes mellitus increase gingival crevicular fluid (GCF) levels of prostaglandin E₂ (PGE₂), interleukin-1beta (IL-1ß), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-2 (PAI-2).Design and methodsSeventeen type 2 diabetic patients with periodontal disease (DM), 17 otherwise healthy periodontally diseased patients (PD) and 17 systemically and periodontally healthy control subjects (H) were enrolled. Clinical periodontal measurements were recorded at six sites/tooth. GCF samples were analyzed by ELISA. Data were tested by statistical tests.ResultsDM group revealed lower IL-1ß levels than PD group (p < 0.01). PGE₂, t-PA and PAI-2 levels were similar in DM and PD groups (p > 0.05). PGE₂, t-PA levels were higher in DM and PD groups than H group (p < 0.05). PAI-2 level was higher in DM group than H group (p < 0.05). GCF total amount of PGE₂ in DM group exhibited significant correlations with all clinical periodontal measurements (p < 0.05).ConclusionType 2 diabetes in this study seems not to increase GCF levels of the evaluated inflammatory mediators.     

A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population

BackgroundLRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimer's disease (AD). Recently, one genome-wide association study has revealed that the rs3755166 (G/A) polymorphism located in the LRP2 promoter is associated with development of AD in Caucasians, while there are no studies on the association LRP2 of with AD risk in Asians.MethodsTo evaluate the relationship between the rs3755166 polymorphism of the LRP2 gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 361, age > 50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of LRP2 (rs3755166) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD.ResultsThe prevalence of the minor allele (A) in the rs3755166 polymorphism was significantly different in AD patients and control subjects (P < 0.05). The rs3755166 polymorphism was associated with AD in the ethnic Chinese Han (OR = 1.378, 95% CI: 1.017-1.867, P = 0.039), and the results were not influenced by age, gender, or APOE status (P = 0.441, P = 0.94, P = 0.432, respectively).ConclusionOur data revealed the allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to AD risk in the Chinese Han Population.     

The RANTES gene promoter polymorphisms are associated with the risk of atherothrombotic cerebral infarction in Northern Han Chinese

BackgroundRegulated upon activation, normal T-cell expressed and secreted (RANTES) plays an important role in the inflammatory process. This study is aimed at evaluating the potential association of the ? 403G/A (rs2107538) and ? 28C/G (rs2280788) polymorphisms of the RANTES gene promoter with the risk of atherothrombotic cerebral infarction (ACI) in Northern Han Chinese.MethodA total of 314 patients with ACI and 389 unrelated aged-matched healthy controls were recruited. Their genotypes of the RANTES gene promoter ? 403G/A (rs2107538) and ? 28C/G (rs2280788) were analyzed by multiplex polymerase chain reaction (multiplex PCR) and multiplex SNaPshot analysis. The potential association of genotyping and allele frequencies with ACI in this population was assessed statistically.ResultsThe frequencies of ? 403AA genotype and A allele in ACI male patients were significantly higher than that in healthy controls (P = 0.007, P = 0.009, respectively). Female patients were not different. Multiple logistic regression analysis revealed that the ? 403AA genotype in males was significantly associated with an increased risk of ACI, even after adjusting for confounding factors (OR = 4.344; 95% CI = 1.969–9.582; P < 0.001). Although there was no significant association of the ? 28C/G polymorphism with ACI, the A-₄₀₃C-₂₈ haplotype was significantly associated with an increased risk of ACI in Han Chinese [OR = 1.56, 95% CI = 1.23–1.98, P < 0.001].ConclusionsOur data suggest that the ? 403AA genotype and A allele of the RANTES promoter were associated with increased risk for the development of ACI in male Northern Han Chinese.     

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.     

The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta-analysis of 1938 cases and 1990 controls

ObjectivesGenetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD.Design and methodsTwo investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0.Results5 case–control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR = 0.595, 95%CI = 0.298–1.188, P = 0.141; G/G vs G/A + A/A: OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G/G + G/A vs A/A: OR = 0.611, 95%CI = 0.334–1.119, P = 0.111; OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G vs A: OR = 0.843, 95%CI = 0.675–1.053, P = 0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P = 0.008, P = 0.021, P = 0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity.ConclusionsOur meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.