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PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

ABSTRACT: A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg's and Egger's test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies.

SUBMITTER: Xu K

PROVIDER: S-EPMC3818463 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

Xu Kuanfeng K Liu Xiaoyun X Yang Fan F Cui Dai D Shi Yun Y Shen Chong C Tang Wei W Yang Tao T

PloS one 20131105 11

A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses w ...[more]

PMID: 24223897

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Project description:BackgroundA number of studies were carried out to assess the association of angiotensin I converting enzyme (ACE) I/D and plasminogen activator inhibitor-1 (PAI-1-1) 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus (T2DM). However, there are a few studies in Iranian patients with T2DM. Here, we tested for an association of ACE I/D and PAI-1 4G/5G polymorphisms with T2DM risk.MethodsOne hundred-eighteen patients with T2DM and 125 healthy subjects were participates in this study. The ACE I/D (rs4340) and PAI-1 4G/5G (rs1799889) polymorphisms was genotyped by conventional and PCR-RFLP assays, receptively. The associations was evaluated by calculating the odds ratio (OR) and 95% confidence interval (95% CI).ResultsThe genotype distribution of ACE I/D and PAI-1 4G/5G polymorphisms were not deviated from the Hardy-Weinberg equilibrium in healthy controls. The ACE II, ID, and DD genotype frequencies were 18.6%, 48.3%, and 33.1% in the T2DM patients versus 24.0%, 45.6% and 30.4% in healthy subjects, respectively. The PAI-1 4G/4G, 4G/5G, and 5G/5G genotype frequencies were 16.9%, 51.7%, and 31.4% in cases versus 24.8%, 57.6% and 17.6% in controls, respectively. There is a significant distribution in genotype/allele of PAI-1 4G/4G between cases with T2DM and healthy control, but not for ACE I/D. Moreover, the 5G/5G genotype is significantly (OR = 2.139, CI 95% 1.171-3.907, p = 0.013) increased the risk of T2DM by two folds in the cases than healthy controls.ConclusionsOur findings suggest that PAI-1 4G/5G may be likelihood risk factor for the development of T2DM in the Iranian patients. The higher frequency of PAI-1 5G/5G genotype in patients with T2DM revealed that individuals with the 5G allele may be at higher risk of T2DM development than those with 4G. However, there was no significant association between ACE I/D polymorphism and T2DM in our population. Future rigorous, well-designed studies with larger sample should replicate this study to confirm our findings in Iranian T2DM patients.

Project description:BackgroundVenous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE.MethodsA total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously.ResultsThe TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group.ConclusionThe PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.

Dataset Information

PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

Publications

PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

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