Association of angiotensin converting enzyme and plasminogen activator inhibitor-1 promoter gene polymorphisms with features of the insulin resistance syndrome in patients with premature coronary heart disease

Viitanen, Laura; Pihlajamäki, Jussi; Halonen, Pirjo; LEHTONEN, M; Kareinen, Anu; Lehto, Seppo; Laakso, Markku

doi:10.1016/s0021-9150(00)00705-x

Cited by 40 publications

(19 citation statements)

References 28 publications

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“…An association of the 4G allele with higher PAI-1 levels/antigen has been shown in patients with coronary artery disease, 2,3 patients with diabetes mellitus, 7 healthy subjects, 4 and postmenopausal women, 5 whereas only a weak relation was found in healthy women but not men, 42 and no association was found in patients 6 or first-degree relatives of patients with type 2 diabetes, 43 in healthy men, 44 or in families with premature and severe coronary heart disease. 45 Differences in the study populations with regard to factors affecting PAI-1 levels or the relation of the 4G/5G genotype and PAI-1, such as gender, 42 various underlying disease conditions (coronary artery disease, diabetes mellitus, and insulin resistance), 46 and concomitant medications, such as estrogen replacement therapy 5 or drugs that affect the reninangiotensin-aldosterone system, 5,46 may account for these differences to some extent. Furthermore, ethnicity may be a contributing factor, as described previously in AfroCaribbeans, Asians, Pima Indians, Japanese, and, more recently, blacks.…”

Section: Discussionmentioning

confidence: 99%

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

et al. 2003

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Background-The 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene has been related to cardiovascular disease. Methods and Results-Insulin resistance was measured with a frequently sampled intravenous glucose tolerance test in the Insulin Resistance Atherosclerosis Study (IRAS), and PAI-1 4G/5G promoter genotype was established by allelespecific polymerase chain reaction amplification of genomic DNA. There were 287 subjects with the 4G/4G genotype (18.4%), 691 heterozygote subjects (44.2%), and 586 carriers of the 5G/5G genotype (37.5%). The genotype distribution was different across the 3 ethnic groups (Pϭ0.001). PAI-1 levels were lower in blacks than in non-Hispanic whites and Hispanics and lower in non-Hispanic whites than in Hispanics (all Pϭ0.0001). Subjects homozygous for the 4G allele had the highest plasma PAI-1, heterozygote subjects were intermediate, and 5G homozygotes had the lowest levels of PAI-1. These patterns remained unaffected by adjustments for age, gender, clinical center, glucose tolerance status, body mass index, waist, triglycerides, and insulin resistance. Multiple linear regression analyses showed that the 4G/5G genotype explained very little of the variation in PAI-1 levels (0.63% in non-Hispanic whites, 0.99% in Hispanics, and 2.37% in blacks), and interaction analyses revealed no significant differences in the relation of circulating PAI-1 levels to the 4G/5G genotype by ethnicity (Pϭ0.4). Conclusions-We have shown ethnic differences in the PAI-1 4G/5G polymorphism along with corresponding differences in circulating PAI-1 levels. The association of the genotype with PAI-1 levels was seen consistently among all 3 ethnic groups and was unaffected by metabolic covariates, including insulin resistance. (Circulation. 2003;107:2422-2427.)

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Section: Discussionmentioning

confidence: 99%

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

et al. 2003

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“…32 Thus, this expression would be greater in omental tissue and would probably be related to the metabolic changes found in the insulin resistance (IR) syndrome. 32 The ACE gene I/D polymorphism genotypes have recently been linked with elements of IR syndrome in patients with premature CHD 33,34 and in the Chinese diabetes type 2 population. 34 Our cross-sectional study includes a group with CHD with higher prevalence of obesity and abdominal fat distribution associated with metabolic risk factors of CHD, common of IR.…”

Section: Discussionmentioning

confidence: 99%

The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease

Riera-Fortuny

Real

Chaves³

et al. 2004

Int J Obes

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OBJECTIVE:To analyse the relation between overweight, obesity and fat distribution with I/D polymorphism of the angiotensinconverting enzyme (ACE) gene and its association with coronary heart disease (CHD). DESIGN: Cross-sectional, case-control study. SUBJECTS: A total of 185 cases (141 males) who had suffered at least one episode of CHD and 182 controls (127 males). MEASUREMENTS: Body mass index, waist circumference, blood pressure, plasma total cholesterol, triglycerides, HDL cholestrol and fasting glucose were measured with standard methods, genotyping the I/D polymorphism of ACE gene. RESULTS: Obesity and abdominal fat deposit are associated with CHD in women, but not independently. We have found an association between obesity and abdominal fat deposit with the ACE gene I/D polymorphism in subjects with CHD. Subjects with CHD and DD or ID genotypes have significantly higher prevalence of obesity and abdominal fat deposit and higher values of weight and waist circumference. In addition, the DD and ID genotypes increased crude OR of obesity. The DD and ID genotypes of the ACE gene I/D polymorphism and BMI are independently associated with CHD. CONCLUSION: There is a relation between the type and grade of obesity with the genotypes of the ACE gene I/D polymorphism in subjects with CHD.

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“…Moreover, fasting insulin levels, triglycerides and BMI have also been associated with the 4G/5G in subjects with hyperlipidaemia and premature coronary disease or non-insulin-dependent diabetes in Caucasians [24,37,38], but not in all tested populations [39,40]. Recently, an association was found for the 4G/5G variant with obesity in a Scandinavian population [41], but these results were not further confirmed [42,43].…”

Section: Discussionmentioning

confidence: 99%

PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population

et al. 2003

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Aim/hypothesis. Plasminogen activator inhibitor-1 (PAI-1) is a main regulator of the endogenous fibrinolytic system and modulates the thrombosis progression. We analyzed genetic contributions of PAI-1 mutations to the metabolic syndrome and to its complications. Methods. PAI-1 promoter and coding sequences were screened for mutations. Genotypes were determined for 1067 unrelated individuals of a French Caucasian cohort, selected for diabetes and obesity. Association between PAI-1 polymorphisms and phenotypes related to metabolic syndrome were statistically studied.Results. There were five variants identified: two common polymorphisms, −765 4G/5G and −844A>G, in the promoter, and three new non-synonymous SNPs, Ala15Thr, Val17Ile and Asn195Ile. In obese non-diabetic subjects, the two promoter polymorphisms were associated with higher fasting glucose concentrations (p=0.006 andp=0.0004, for −765 4G/5G and −844 A>G, respectively) and insulin (p=0.05 and p=0.008, for −765 4G/5G and −844 A>G, respectively). Moreover, the −844 A>G SNP was associated with lower triglyceride (p=0.002) and higher HDL cholesterol concentrations (p=0.02) in lean subjects. In addition, the two promoter and Ala15Thr polymorphisms showed a trend towards association with CHD in diabetic subjects (-765 4G/5G: 0.56/0.51, p=0.05; −844A>G: 0.63/0.57, p=0.02; Ala15Thr: 0.91/0.88, p=0.04). The SNPs Ala15Thr, located in the PAI-1 signal peptide, and rare the Asn195Ile, located in a β-sheet structure, could influence conformation of these two structures. Conclusions/interpretation. Our results support the hypothesis that PAI-1 polymorphisms probably interact with known environmental risk factors (chronic hyperglycaemia, obesity, etc.) to induce a more severe insulin-resistant metabolic profile in overweight subjects, and to further increase risk for CHD in diabetic subjects. [Diabetologia (2003[Diabetologia ( ) 46:1284[Diabetologia ( -1290 Keywords PAI-1, obesity, metabolic syndrome, CHD, fasting glucose, insulin, triglycerides, HDL, Type 2 diabetes mellitus.

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Association of angiotensin converting enzyme and plasminogen activator inhibitor-1 promoter gene polymorphisms with features of the insulin resistance syndrome in patients with premature coronary heart disease

Cited by 40 publications

References 28 publications

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

The relation between obesity, abdominal fat deposit and the angiotensin-converting enzyme gene I/D polymorphism and its association with coronary heart disease

PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic Caucasian population

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