Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.
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PMID:Myocardial infarction in a 35-year-old man with homocysteinemia, high plasminogen activator inhibitor activity, and resistance to activated protein C. 943 45

The factor II G20210A mutation is a recently identified congenital risk factor for venous thrombosis. Its role in artery disease is still undefined. We investigated 72 patients (35 male and 37 female) with documented ischemic stroke occurred before 50 years of age and without risk factors such as diabetes, hypertension, and hyperlipidemia; 198 thrombosis-free individuals were investigated as the control group. We found 7 heterozygotes (9.7%) and 2 homozygotes (2.7%) for the mutant factor II allele among the patients and 5 heterozygotes (2.5%) among the controls; the mutant factor II allele frequency in the patient group (7.6%, 95% confidence interval [CI], 3.3 to 11.9) was significantly higher than in the controls (1.2%; 95% CI, 0.1 to 2.3; P = .0001). The prevalence of other investigated mutant alleles (factor V G1691A, methylenetetrahydrofolate reductase C677T) did not significantly differ between the two groups. The odds ratio for ischemic stroke associated with the carriership of the mutant factor II allele (both heterozygous and homozygous genotypes) was 5.1 (95% CI, 1.6 to 16.3). Heterozygous genotype was associated with a 3.8-fold increased risk for cerebral ischemia (95% CI, 1.1 to 13.1); in particular, assuming an expected prevalence of homozygotes in the general population of 1.6 to 10,000 according to the Hardy-Weinberg equilibrium, the risk associated with the homozygous genotype was estimated exceedingly high, being increased 208-fold.
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PMID:Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic disease in young patients. 957 89

The missense mutation in the 677th nucleotide (C677T) of methylenetetrahydrofolate reductase gene causes substitution of valine (V) for alanine (A) resulting in three genotypes VV, VA and AA. The VV genotype causes hyperhomocysteinemia and may be a risk factor for coronary artery disease. We determined genotypes by polymerase chain reaction and subsequent restriction fragment length analysis and compared them in 84 patients with type 2 diabetes and in 115 non-diabetic subjects with and without coronary disease. Fractional urinary excretion rate of albumin was assessed by nephelometry. The VV, VA, and AA frequencies in the diabetic and in the control groups were 0.095, 0.357, 0.548 and 0.061, 0.417, 0.522, respectively (p = NS, diabetic vs. controls, chi2 test). Genotype frequencies did not differ in either diabetic or control subjects between those with or those without coronary disease (chi2 test). The fractional urinary excretion rate of albumin (mean +/-SD) in diabetic patients with the VV genotype i.e. 1.59 +/-0.71 was lower (Kruskall-Wallis test p = 0.002) than in the other genotypes i.e. VA 5.98 +/-9.75 and AA 3.75 +/-4.77, respectively (post-hoc Mann-Whitney test VV vs. VA p = 0.005 and VV vs. AA p = 0.054, respectively). We found that in patients with type 2 diabetes the methylenetetrahydrofolate reductase VV genotype was associated with a low urinary albumin excretion but not with coronary artery disease or diabetes per se.
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PMID:Mutation C677T of methylenetetrahydrofolate reductase gene is not associated with coronary artery disease, but possibly with albuminuria, in type 2 diabetic patients. 980 73

Several recent studies evaluated a possible effect of the prothrombotic polymorphisms such as 5,10 methylenetetrahydrofolate reductase (MTHFR) nt 677C --> T, factor V (F V) nt 1691G --> A (F V Leiden), and factor II (F II) nt 20210 G --> A on the risk of myocardial infarction. In the present study, we analyzed the effect of these prothrombotic polymorphisms, as well as apolipoprotein (Apo) E4, smoking, hypertension, diabetes mellitus, and hypercholesterolemia, on the risk of myocardial infarction in young males. We conducted a case-control study of 112 young males with first acute myocardial infarction (AMI) before the age of 52 and 187 healthy controls of similar age. The prevalences of heterozygotes for F V G1691A and F II G20210A were not significantly different between cases and controls (6.3% v 6.4% and 5.9% v 3.4% among cases and controls, respectively). In contrast, the prevalence of MTHFR 677T homozygosity and the allele frequency of Apo E4 were significantly higher among patients (24.1% v 10.7% and 9.4% v 5.3% among cases and controls, respectively). Concomitant presence of hypertension, hypercholesterolemia, or diabetes and one or more of the four examined polymorphisms increased the risk by almost ninefold (odds ratio [OR] = 8.66; 95% confidence interval [CI], 3.49 to 21.5) and concomitant smoking by almost 18-fold (OR = 17.6; 95% CI, 6.30 to 48.9). When all atherogenic risk factors were analyzed simultaneously by a logistic model, the combination of prothrombotic and Apo E4 polymorphisms with current smoking increased the risk 25-fold (OR = 24.7; 95% CI, 7.17 to 84.9). The presented data suggest a synergistic effect between atherogenic and thrombogenic risk factors in the pathogenesis of AMI, as was recently found in a similar cohort of women.
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PMID:Synergistic effects of prothrombotic polymorphisms and atherogenic factors on the risk of myocardial infarction in young males. 1009 Sep 25

We retrospectively examined the relationship between the genotype of the angiotensin-converting enzyme (ACE) gene or the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, and the secondary cardiac events after myocardial infarction. The study population consisted of 176 patients (ACE genotype: deletion homozygote (DD)=20, insertion/deletion heterozygote (ID)=91, insertion homozygote (II)=65; MTHFR genotype: valine homozygote (VV)=37, valine/alanine heterozygote (VA)=71, alanine homozygote (AA)=68) with acute or recent myocardial infarction at the start of the follow-up. We defined the occurrence of cardiac death, recurrent myocardial infarction, or admission due to unstable angina as the endpoint. Cardiac events related coronary intervention were excluded from the endpoints. During the follow-up (1903+/-1414 days), four patients had cardiac death, 12 patients had recurrent myocardial infarction and 13 patients had admission due to unstable angina. A Cox analysis revealed that the endpoints were significantly associated with diabetes mellitus (RR=4.423), total cholesterol level (RR=1.025) and the genotype of the ACE gene (RR=4.490). The ID or DD genotype of the ACE gene was associated with higher occurrence of the endopoints. The MTFHR gene was not associated with the endopoint. The present results suggest that the presence of the deletion allele of the ACE gene may be a risk factor for secondary cardiac events after myocardial infarction.
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PMID:D allele of the angiotensin-converting enzyme gene is a risk factor for secondary cardiac events after myocardial infarction. 1045 99

Thrombophilia is now considered a multicausal disease, with an interplay of acquired and genetic risk factors. Recent studies have shown that patients with the 20210 A prothrombin mutation display remarkably similar characteristics compared with patients with Factor V Leiden mutation. It is evident that neither the Factor V Leiden mutation nor the 20210 A prothrombin mutation is a major risk factor for myocardial infarction or stroke, unless accompanied by other classical risk factors, including diabetes mellitus, hypertension and smoking. Finally, the homozygous form of the thermolabile methylenetetrahydrofolate reductase gene, although leading to elevated homocysteine levels, seems not to represent a genetic risk factor for venous thrombosis.
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PMID:Thrombophilia. 1046 43

We assessed the contribution of serum homocysteine levels, an independent risk factor for vascular disease, and of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation to the variability of carotid intimal-medial thickness (IMT) in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ninety-five patients (33 males and 62 females, mean age 53 +/- 10 years) without nephropathy or other vascular complications were enrolled. Fasting total serum homocysteine and other biochemical analytes were measured. The MTHFR polymorphism was determined by the polymerase chain reaction. Common carotid IMT and plaques or stenoses in the carotid district were measured by ultrasonography. Serum total homocysteine concentrations were higher in subjects with the mutant (Val/Val) genotype than in those with the Ala/Val plus Ala/Ala genotypes (P = 0.02). On univariate analysis, carotid IMT was significantly associated with age, body mass index (BMI), systolic blood pressure, and total cholesterolemia. No significant association was found between IMT and serum homocysteine or the MTHFR polymorphism, although a slightly greater IMT was observed in the homozygous Val genotypes. On multiple regression analysis, only age and BMI were independently associated with IMT and explained about 40% of IMT variability. The results did not change when the analysis was restricted to the subgroups with or without atherosclerotic plaques in the carotid district. In 95 Italian NIDDM patients without nephropathy, neither basal levels of serum total homocysteine nor the MTHFR C677T polymorphism predicted significant changes in common carotid intimal-medial thickness.
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PMID:Serum homocysteine, MTHFR gene polymorphism, and carotid intimal-medial thickness in NIDDM subjects. 1050 Mar 10

From July 1997 to June 1998, a total of 1323 subjects, including 1180 controls, 94 patients with diabetes mellitus, and 49 patients with deep-vein thrombosis, varying in age and gender, were consecutively entered into our study. Their mean (+/- SD) age was 50.0 +/- 18.0 years, range 1-99 years; 930 were male and 393 were female. None of the subjects was found to have abnormal prothrombin 20210A allele mutation. In total, 150 subjects (11.3%) were found to have a homozygous 677 C-->T mutation of the methylenetetrahydrofolate reductase gene, in which 125 were controls (10.6%), 17 were diabetics (18.1%) and 8 were patients with deep-vein thrombosis (16.3%). However, 524 subjects (39.6%) were found to have a heterozygous methylenetetrahydrofolate reductase 677 C-->T mutation. We suggested that the Chinese race dose not have the prothrombin 20210A allele, but can carry the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene.
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PMID:Prevalence of prothrombin 20210A allele and methylenetetrahydrofolate reductase C677T genetic mutations in the Chinese population. 1087 Apr 77

The methylenetetrahydrofolate reductase (MTHFR) gene polymorphism has been shown to be associated with cardiovascular disease in healthy subjects as well as in patients with end-stage renal disease (ESRD). In this study, we examined the allelic frequency and genotype distribution of the MTHFR gene in 151 Chinese ESRD patients receiving hemodialysis and 135 healthy controls. In addition, we investigated the relationship between the MTHFR gene polymorphism and the plasma homocysteine (Hcy) level as well as the intima-media thickness of common carotid artery (CC-IMT) in these patients. The allelic frequency of the MTHFR gene with the C677T mutation in ESRD patients was 24.5% and that in healthy controls was 23%. Mean plasma Hcy level of the ESRD patients (23.1 +/- 7.4 micromol/l) was significantly higher than that of the controls (10.1 +/- 5.0 micromol/l), but did not correlate with vitamin B(6) and vitamin B(12) status. Moreover, the extent of hyperhomocysteinemia was genetically affected by the C677T mutation of the MTHFR gene. The plasma Hcy levels for the patients with the CC, CT and TT genotypes of the MTHFR gene were 22.3 +/- 6.8, 22.8 +/- 7.3, and 28.3 +/- 2.8 micromol/l, respectively. In addition, we found that the patients bearing the TT genotype had the highest CC-IMT (0.93 +/- 0.07 mm), whereas the lowest values (0.79 +/- 0.13 mm) were observed in those who had the CC genotype. One-way ANOVA showed that the CC-IMT in the patients with the TT genotype was significantly greater than that of the patients with the CC genotype (p < 0.05). Moreover, the mean CC-IMT of the patients carrying either TT or CT genotype of the MTHFR gene was significantly higher than that of the patients bearing the CC genotype (0.86 +/- 0.14 vs. 0.79 +/- 0.13 mm, p = 0.002). Multiple regression analysis, in which the change in CC-IMT was used as the dependent variables, identified age, smoking, the MTHFR genotype (CC = 0, CT = 1, TT = 2) and diabetes mellitus as the independent variables significantly associated with the increase of CC-IMT (p < 0.001). These risk factors jointly explained 43.9% of the CC-IMT variation and age explained most of the variation (R(2) = 0.34). We conclude that both the TT genotype and the T allele of the MTHFR gene are associated with the increase of CC-IMT in hemodialysis patients. The C677T mutation of the MTHFR gene may be an independent risk factor that predicts the development of carotid atherosclerosis in ESRD patients.
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PMID:Polymorphism in methylenetetrahydrofolate reductase gene: its impact on plasma homocysteine levels and carotid atherosclerosis in ESRD patients receiving hemodialysis. 1128 60

Increased plasma concentrations of homocysteine have been found in patients with coronary artery disease (CAD) and essential hypertension (EH) and in patients with diabetic complications. The 677C/T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to the MTHFR enzyme activity and to the plasma homocysteine concentration. This study was designed to investigate an association of this polymorphism with CAD, EH, and type II diabetes mellitus in the Czech population. The MTHFR genotypes were assessed by the polymerase chain reaction-based methodology in a sample of 1199 unrelated Caucasian subjects with CAD, EH, type II diabetes, or a combination of these diseases, and in healthy subjects. Allele frequencies of the MTHFR polymorphism differed considerably between women with and without type II diabetes mellitus (P = 0.00069), with a higher frequency of the C allele in the diabetic women. In addition, the MTHFR T allele frequency was significantly higher in normotensive subjects with CAD compared with normotensive subjects without this disease (P = 0.020). Both associations were confirmed by multiple logistic regressions. In conclusion, while the C allele of the 677C/T MTHFR polymorphism is associated with type II diabetes mellitus in women, the T allele is associated with CAD only in normotensive subjects of Czech origin.
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PMID:Methylenetetrahydrofolate reductase polymorphism, type II diabetes mellitus, coronary artery disease, and essential hypertension in the Czech population. 1138 55


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