Dimitri J. Richter

The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction.

Background The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI). Design and methods Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues. Results In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P = 0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR = 0.743, 95% CI = 0.595–0.927, P = 0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P = 0.856), or in multivariate analysis adjusted for the same confounders (RR = 0.743, 95% CI = 0.473–1.167, P = 0.197). Conclusions Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.

Lipoprotein lipase gene variants relate to presence and degree of microalbuminuria in Type II diabetes.

AbstractAims/hypothesis. Lipids and lipoproteins, particularly triglyceride rich lipoproteins, could influence the development and progression of microalbuminuria in diabetes. Lipoprotein lipase gene variants have been found to correlate with lipid/lipoprotein concentrations, especially hypertriglyceridaemia. We assessed the influence of this gene on microalbuminuria in Type II (insulin-dependent) diabetes mellitus. Methods. Microalbuminuria was determined quantitatively in 386 sequential Type II diabetic patients by measurement of the albumin-to-creatinine ratio (ACR). DNA was analysed for two common intronic LPL single nucleotide polymorphisms (Pvu II, intron 6, and Hind III, intron 8), and three common exonic mutations (Asp9-Asn, exon 2, Asn291-Ser, exon 6, and Ser447-Ter, exon 9). Results. Individuals with P2P2 (Pvu II) and H2H2 (Hind III) genotypes had significantly greater ACRs (P2P2 vs P1P1+P1P2, 5.0±0.5 vs 3.4±0.3, p=0.0004 and H2H2 vs H1H1+H1H2, 4.3±0.4 vs 3.4±0.3, p=0.04). Logistic regression analysis demonstrated that only the P2P2 genotype (p=0.0004), systolic BP (p=0.008) and creatinine (p=0.031) were independently associated with the presence of microalbuminuria/proteinuria. P2 homozygotes were 170% more likely to have microalbuminuria or proteinuria, O.R. 2.7 (1.6–4.5, p=0.0001), 150% more likely to have microalbuminuria, O.R. 2.5 (1.5–4.3, p=0.001), and 330% more likely to have proteinuria, O.R. 4.3 (1.6–11.4, p=0.004). There were no associations of microalbuminuria with any of the exonic polymorphisms. Conclusion/interpretation. Genetic variants of lipoprotein lipase correlate with presence and severity of microalbuminuria in Type II diabetes, independent of effect on serum lipids. This association is only apparent in genetic variants demonstrating greatest heterozygosity.

Lack of Association between Common Polymorphisms in Genes of the Renin-Angiotensin System and Mortality after Myocardial Infarction

The insertion/deletion (I/D) polymorphism in the ACE gene and the A1166C polymorphism in the AT1R gene have been associated with left ventricular remodelling and prognosis after acute myocardial infarction (AMI). We investigated whether these genetic variants associate with impaired left ventricular ejection fraction (LVEF) and increased risk for in-hospital mortality after AMI. Consecutive AMI patients were recruited on admission and were genotyped for the above-mentioned polymorphisms. The frequency of the studied genotypes did not differ significantly between deceased patients and those who survived. The LVEF did not differ among patients with or without the DD genotype (45 ± 10 vs. 45 ± 10%, p = 0.892) or the CC genotype (45 ± 10 vs. 46 ± 10%, p = 0.859). These data question the role of the studied genotypes in the pathogenesis of AMI and do not support the previously supported hypothesis that these genotypes influence prognosis after AMI.

OMEGA-3 POLYUNSATURATED FATTY ACID SUPPLEMENTS DOSE AND CARDIOVASCULAR EVENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Initial studies on omega-3 polyunsuturated fatty acids (PUFAs) showed promising results on cardiovascular (CV) events. However, recent studies reported controversial Results. We aimed to perform a meta-analysis of all randomized studies that used omega-3 PUFA supplements and investigate their effect