Project description:ContextCoronary artery disease (CAD) is one of the common diseases in patients with type two diabetes mellitus (T2DM). The nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPARγ) plays a vital role in dyslipidemia, and oxidative stress is involved in atherogenesis.ObjectiveThe study aimed to determine the association between Pro12Ala polymorphism of the PPARγ2 gene(rs1801282) and CAD risk in T2DM patients in the Iranian population.DesignA group of 145 T2DM patients with a history of CAD were enrolled, together with 145 sex and gender-matched individuals who had neither CAD nor history of T2DM who were enrolled in a case-control study.Subjects and methodsPolymerase chain reaction-restriction fragment length polymorphism technique was applied to genotype the PPARγ2 gene polymorphisms. Statistical analysis was done using SPSS version 22.ResultsCC and GC genotypes of Pro12Ala had a higher frequency in the control and case groups, respectively. The GC genotype was associated with a significantly increased CAD risk compared to the CC genotype (adjusted OR= 2.66, 95% CI = 1.5-29.5, p<0.01). The mean triglycerides and total cholesterol level were significantly higher in the CC genotype than the GC genotype in both case and control groups (p<0.05). The mean level of fasting blood glucose was significantly higher in the CC genotype compared to GC genotype in the case group (p<0.05). The mean of creatinine, lipid profiles, microalbuminuria, and hemoglobin A1c had no significant difference between CC and GC genotypes in both groups (p>0.05).ConclusionPPARγ2 Pro12Ala polymorphism could be an essential indicator for the increased risk of CAD in the Iranian people with T2DM.
Project description:A common allele on chromosome 9p21 has been repeatedly associated with increased risk of coronary artery disease (CAD) in the general population. However, the magnitude of this effect in the population with diabetes has not been well characterized.To examine the association of the 9p21 variant with CAD in individuals with type 2 diabetes and evaluate its interaction with poor glycemic control.(1) Case-control study of 734 type 2 diabetes patients (322 with angiographically diagnosed CAD and 412 with no evidence of CAD) who were recruited between 2001 and 2006 at the Joslin Clinic, Beth Israel Deaconess Medical Center; and (2) independent cohort study of 475 type 2 diabetes patients from the Joslin Clinic whose survival status was monitored from their recruitment between 1993 and 1996 until December 31, 2004. Participants for both studies were genotyped for a representative single-nucleotide polymorphism at 9p21 (rs2383206) and characterized for their long-term glycemic control by averaging multiple hemoglobin A(1c) (HbA(1c)) measurements taken in the years before study entry.For the case-control study, association between single-nucleotide polymorphism rs2383206 and CAD defined as angiographically documented stenosis greater than 50% in a major coronary artery or a main branch thereof was assessed and for the cohort study, cumulative 10-year mortality was documented.Individuals who were homozygous for the risk allele were significantly more frequent among case than control participants (42.3% vs 28.9P = .0002). This association was unaffected by adjustment for cardiovascular risk factors, but the effect of the risk genotype was significantly magnified (adjusted P for interaction = .048) in the presence of poor glycemic control (worst tertile of the distribution of HbA(1c) at examination). Relative to the CAD risk for patients with neither a 9p21 risk allele nor poor glycemic control, the CAD odds for participants having 2 risk alleles but not poor glycemic control were increased 2-fold (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.17-3.41), whereas the odds for study participants with the same genotype and with poor glycemic control were increased 4-fold (OR, 4.27; 95% CI, 2.26-8.01). The interaction was stronger (adjusted P = .005) when a measure of long-term glycemic control (7-year average rather than most recent HbA(1c)) was used with ORs of 7.83 (95% CI, 3.49-17.6) for participants having 2 risk alleles and a history of poor glycemia and 1.54 (95% CI, 0.72-3.30) for participants with the same genotype but without this exposure. A similar interaction between 9p21 variant and poor glycemic control was observed with respect to cumulative 10-year mortality in the cohort study (43.6% in patients with 2 risk alleles and poor glycemic control, 23.1% in individuals with only the 2 risk alleles, 30.0% in individuals with only poor glycemic control, and 31.6% in individuals with neither factor, P for interaction, = .036).In this study population, the CAD risk associated with the 9p21 variant was increased in the presence of poor glycemic control in type 2 diabetes.
Project description:Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
Project description:AbstractCardiovascular disease (CAD) is a devastating illness, but to date there are limited means of predicting a person's coronary stenosis severity and their prognosis. The study was performed to investigate the relationship between dipeptidyl peptidase 4(DPP4) gene polymorphisms and serum lipid profiles, as well as the severity of coronary artery stenosis in patients with CAD and type 2 diabetes (T2DM) for the first time.Herein, 201 patients with CAD and T2DM were enrolled in the Department of Cardiology, Shandong Provincial Qianfoshan Hospital. DPP4 rs3788979 and rs7608798 single nucleotide polymorphisms (SNPs) were genotyped. The general information of all patients was collected, and the associations between DPP4 SNPs and lipid profiles were detected. At the same time, association between SNP polymorphisms and the degree of coronary artery stenosis were analyzed.There was a significant difference in apolipoprotein B (ApoB) levels (P = .011) for the rs3788979 polymorphism, while no difference was identified in other blood lipids or with other mutations. SNP mutation of A to G in rs3788979 was associated with a reduced percentage of severe coronary artery stenosis in female patients (P = .023) as well as those with nosmoking (P = .030), nodrinking (P = 0.007), and nocardiovascular family history (P = 0.015).G allele of rs3788979 is associated with a reduced ApoB level. Besides, we suggest that G allele in rs3788979 may have a cardioprotective effect and prove to be a useful and specific measure when predicting a patient's coronary stenosis severity if diagnosed with CAD and T2DM.
Project description:Coronary artery disease (CAD) is a common complication of Type 2 diabetes mellitus (T2DM). Understanding the pathogenesis of this complication is essential in both diagnosis and management. Thus, this study aimed to characterize the presence of CAD in T2DM using molecular markers and pathway analyses. Total RNA from peripheral blood mononuclear cells (PBMCs) underwent whole transcriptomic profiling using the Illumina HumanHT-12 v4.0 expression beadchip. Differential gene expression with gene ontogeny analyses was performed, with supporting correlational analyses using weighted correlation network analysis (WGCNA)
Project description:BackgroundPrevious studies have investigated the association between the haptoglobin rs72294371 polymorphism and coronary artery disease (CAD) risk, but the results are controversial and uncertain. Therefore, this study aimed to systematically review the literature on haptoglobin polymorphism and susceptibility to CAD.MethodsPubMed, Embase, Web of Science, Cochrane Library, and Wanfang databases were used to identify relevant studies from their inception to April 2024. The pooled odds ratio (OR) with corresponding 95% confidence interval (CI) were used to assess the strength of the association. An OR value greater than one suggested an increased risk; otherwise, it suggested a protective risk.ResultsA total of 15 studies comprising 8,632 individuals (2,988 cases and 5,644 controls) were included. In the current meta-analysis, a significant association between haptoglobin polymorphism and CAD was found under recessive model (OR:0.74, 95% CI:0.60-0.92), dominant model (OR: 0.82, 95% CI: 0.71-0.95), homozygote model (OR: 0.70, 95% CI: 0.53-0.92), and allelic genetic model (OR: 0.80, 95% CI: 0.69-0.94). In the analysis stratified by ethnicity, a statistically significant association was observed in Asians rather than Caucasian population.ConclusionThis meta-analysis indicates that haptoglobin polymorphism is associated with CAD susceptibility, especially in Asians.
Project description:BackgroundColesteryl ester transfer protein (CETP) plays a key role in the metabolism of lipoproteins; therefore, polymorphisms of its gene can affect susceptibility to coronary artery disease (CAD) in diabetes mellitus. The aim of the present study was to investigate association between I405V polymorphism of CETP gene and risk of CAD in patients with type 2 diabetes mellitus.MethodsThe current case-control study was conducted on 143 patients with type 2 diabetes and angiographically diagnosed CAD and 150 patients with type 2 diabetes and without CAD. Genotyping was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The presence of CAD was defined as higher than 50% reduction in coronary artery diameter.ResultsThe genotype frequencies of I405V polymorphism were II (27.3% vs. 23.2%), IV (61.5% vs. 67.5%), and VV (11.2% vs. 9.3%) in diabetic with CAD compared to diabetic without CAD (χ2 = 1.164) (P = 0.55). The I and V alleles were found at frequencies of 63.6% and 61.6% in the diabetic with CAD group and 36.4% and 38.4% in the diabetic without CAD group (χ2 = 0.263) (P = 0.60). No significant difference was observed between two groups in terms of genotype and allele frequency. Moreover, no significant association was observed between II, IV, and VV genotypes and lipid profiles in both groups. However, a significant difference was observed between genotype distributions of I405V polymorphism in men according to the severity of CAD.ConclusionIt is speculated that I405V polymorphism may be associated with the severity of coronary artery stenosis only in men with type 2 diabetes mellitus.
Project description:ObjectiveAdiponectin receptor 1 (encoded by ADIPOR1) is one of the major adiponectin receptors, and plays an important role in glucose and lipid metabolism. However, few studies have reported simultaneous associations between ADIPOR1 variants and type 2 diabetes (T2D), coronary artery disease (CAD) and T2D with CAD. Based on the "common soil" hypothesis, we investigated whether ADIPOR1 polymorphisms contributed to the etiology of T2D, CAD, or T2D with CAD in a Northern Han Chinese population.MethodsOur multi-disease comparison study enrolled 657 subjects, including 165 with T2D, 173 with CAD, 174 with both T2D and CAD (T2D+CAD), and 145 local healthy controls. Six ADIPOR1 single nucleotide polymorphisms (SNPs) were genotyped and their association with disease risk was analyzed.ResultsMulti-case-control comparison identified two ADIPOR1 variants: rs3737884-G, which was simultaneously associated with an increased risk of T2D, CAD, and T2D+CAD (P-value range, 9.80×10(-5)-6.30×10(-4); odds ratio (OR) range: 1.96-2.42) and 16850797-C, which was separately associated with T2D and T2D+CAD (P-value range: 0.007-0.014; OR range: 1.71-1.77). The risk genotypes of both rs3737884 and 16850797 were consistently associated with common metabolic phenotypes in all three diseases (P-value range: 4.81×10(-42)-0.001). We observed an increase in the genetic dose-dependent cumulative risk with increasing risk allele numbers in T2D, CAD and T2D+CAD (P trend from 1.35×10(-5)-0.002).ConclusionsOur results suggest that ADIPOR1 risk polymorphisms are a strong candidate for the "common soil" hypothesis and could partially contribute to disease susceptibility to T2D, CAD, and T2D with CAD in the Northern Han Chinese population.