23 research outputs found
RAS gene polymorphisms, classical risk factors and the advent of coronary artery disease in the Portuguese population
<p>Abstract</p> <p>Background</p> <p>Several polymorphisms within the renin-angiotensin system cluster of genes have been associated with the advent of coronary artery disease (CAD) or related pathologies. We investigated the distribution of 5 of these polymorphisms in order to find any association with CAD development and distinguish if any of the biochemical and behavioural factors interact with genetic polymorphisms in the advent of the disease.</p> <p>Methods</p> <p><it>ACE </it>I/D (rs4340), <it>ACE </it>A11860G (rs4343), <it>AT1R </it>A1166C (rs5186), <it>AGT </it>T174M (rs4762) and <it>AGT </it>M235T (rs699) gene polymorphisms were PCR-RFLP analysed in 298 CAD patients and 510 controls from Portugal. Several biochemical and behavioural markers were obtained.</p> <p>Results</p> <p><it>ACE </it>I/D DD and <it>ACE</it>11860 GG genotypes are risk factors for CAD in this population. The simultaneous presence of <it>ACE </it>I/D I and <it>ACE</it>11860 A alleles corresponds to a significant trend towards a decrease in CAD incidence. We found several synergistic effects between the studied polymorphisms and classical risk factors such as hypertension, obesity, diabetes and dyslipidaemia: the presence of the DD genotype of <it>ACE </it>I/D (and also <it>ACE</it>11860 GG) increases the odds of developing CAD when associated to each one of these classical risk factors, particularly when considering the male and early onset CAD subgroup analysis; <it>AGT</it>235 TT also increases the CAD risk in the presence of hypertension and dyslipidaemia, and <it>AT1R</it>1166 interacts positively with hypertension, smoking and obesity.</p> <p>Conclusion</p> <p><it>ACE </it>polymorphisms were shown to play a major role in individual susceptibility to develop CAD. There is also a clear interaction between RAS predisposing genes and some biochemical/environmental risk factors in CAD onset, demonstrating a significant enhancement of classical markers particularly by <it>ACE </it>I/D and <it>ACE</it>11860.</p
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High fat diet modifies the association of lipoprotein lipase gene polymorphism with high density lipoprotein cholesterol in an Asian Indian population
Background
Single nucleotide polymorphisms (SNPs) in lipoprotein lipase gene (LPL) have been shown to influence metabolism related to lipid phenotypes. Dietary factors have been shown to modify the association between LPL SNPs and lipids; however, to date, there are no studies in South Asians. Hence, we tested for the association of four common LPL SNPs with plasma lipids and examined the interactions between the SNPs and dietary factors on lipids in 1,845 Asian Indians.
Methods
The analysis was performed in 788 Type 2 diabetes cases and 1,057 controls randomly chosen from the cross-sectional Chennai Urban Rural Epidemiological Study. Serum triacylglycerol (TAG), serum total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Dietary intake was assessed using a semi-quantitative food frequency questionnaire. The SNPs (rs1121923, rs328, rs4922115 and rs285) were genotyped by polymerase chain reaction followed by restriction enzyme digestion and 20% of samples were sequenced to validate the genotypes obtained. Statistical Package for Social Sciences for Windows version 22.0 (SPSS, Chicago, IL) was used for statistical analysis.
Results
After correction for multiple testing and adjusting for potential confounders, SNPs rs328 and rs285 showed association with HDL-C (P = 0.0004) and serum TAG (P = 1×10−5), respectively. The interaction between SNP rs1121923 and fat intake (energy %) on HDL-C (P = 0.003) was also significant, where, among those who consumed a high fat diet (28.4 ± 2.5%), the T allele carriers (TT + XT) had significantly higher HDL-C concentrations (P = 0.0002) and 30% reduced risk of low HDL-C levels compared to the CC homozygotes. None of the interactions on other lipid traits were statistically significant.
Conclusion
Our findings suggest that individuals carrying T allele of the SNP rs1121923 have increased HDL-C levels when consuming a high fat diet compared to CC homozygotes. Our finding warrants confirmation in prospective studies and randomized controlled trials
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,
hypercholesterolaemia, 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 M I, either in univariate (6.2 vs.
6.4%, P=0.856), or in multivariate analysis adjusted for the same
confounders (RR = 0.743, 95% Cl = 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. (C) 2004 The European
Society of Cardiology