V minulých letech bylo publikováno mnoho rozporuplných studií týkajících se souvislosti mezi inzerčně-delečním polymorfizmem a renálními a kardiovaskulárními onemocněními. Většina studií podporuje vztah mezi homozygoty pro deleční alelu (DD polymorfizmus) a progresivnějším průběhem některých renálních onemocnění (především IgA nefropatie a diabetické nefropatie). Dále je pravděpodobný vztah mezi nositeli deleční alely a orgánovým poškozením u hypertoniků. Existuje i určitý vztah mezi inzerčně delečním polymorfizmem a terapeutickou odpovědí na inhibitory angiotenzinkonvertujícího enzymu, pravděpodobně v závislosti na pohlaví. Zatím neexistují jednoznač- né vztahy mezi inzerčně delečním polymorfizmem a určitými patofyziologickými mechanizmy.
Many controversial studies concerning relation between angiotensin converting enzyme polymorphism and renal and cardiovascular disease have been published during the last years. Most of the papers have suggested that the DD genotype plays an important negative role in the progression of some renal diseases (e.g. IgA nephropathy, diabetic nepropathy). The D allele may be an independent risk factor for development of the target organ damage in essential hypertension. The therapeutic response on inhibitors of angiotensin converting enzyme depends on insertion-deletion polymorphism. It probably also depends on the gender. The pathological mechanisms of insertion-deletion polymor- phism have not yet been clearly identified.
Východisko. Vysoké hladiny cholesterolu a triglyceridů jsou jako jedny z hlavních rizikových faktorů aterosklerózy ovlivněny jednak faktory genetickými a jednak faktory vnějšího prostředí (dieta, fyzická aktivita). Apolipoprotein CI ovlivňuje transport cholesterolu a triglyceridů ve VLDL částicích. Cílem naší studie bylo objasnit úlohu inzerčního/delečního polymorfizmu v genu pro APOCI v genetické determinaci lipidů u dětí. Metody a výsledky. I/D polymorfizmus v genu pro APOCI byl měřen pomocí řetězové polymerázové reakce s následnou restrikční analýzou PCR produktu restrikčním enzymem HpaI ve dvou skupinách dětí vybraných z opačných částí distribuční křivky cholesterolémií 2000 dětí. Bylo vybráno 82 dětí do vysokocholesterolové skupiny a 86 do nízkocholesterolové skupiny. Nenalezli jsme žádné rozdíly ve frekvencích genotypů APOCI mezi HCG a LCG. V LCG skupině měli jedinci s D/D genotypem výrazně vyšší hladinu LDL cholesterolu než ostatní (p<0,05). V HCG byl trend (p=0,09) mezi APOCI polymorfizmem a LDL cholesterolem opačný, jedinci s D/D genotypem měli nejnižší hladinu LDL cholesterolu. Závěry. Inzerční/deleční polymorfizmus v genu pro APOCI je další z řady polymorfizmů ovlivňujících plazmatické hladiny cholesterolu.
Background. High plasma lipids are one of the risk factor of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been implicated in the development of hyperlipidaemia. Apolipoprotein (apo) CI plays an important role in plasma cholesterol and triglycerides transport by VLDL particles. The aim of the study was to establish the role of the insertion/deletion polymorphism in apoCI gene in the determination of plasma lipids in children. Methods and Results. Using PCR and restriction analysis (HpaI) we have measured I/D polymorphism in APOCI gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high- (HCG) and eighty-six children in low- (LCG) cholesterolemic groups participated on the study. No significant difference was found in the frequencies of the APOCI genotypes or alleles between HCG vs. LCG. Association between LDL cholesterol and genotypes within the LCG was found – the D/D homozygotes have higher lipid level compared to the others (p<0.05). In LCG opposite, but insignificant (p=0.09) trend was observed. Conclusions. The widespread I/D polymorphism in the gene for APOCI determines the plasma lipid levels in childhood and it could become another important genetic marker that plays a role in the genetic determination of cholesterolemia.
- MeSH
- Apolipoproteins C genetics blood MeSH
- Cholesterol blood MeSH
- Child MeSH
- Research Support as Topic MeSH
- Genes MeSH
- Hyperlipidemias diagnosis etiology prevention & control MeSH
- Humans MeSH
- Pediatrics MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Polymorphism, Genetic MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
- Comparative Study MeSH
- MeSH
- Peptidyl-Dipeptidase A genetics MeSH
- Myocardial Infarction MeSH
- Polymerase Chain Reaction MeSH
- Polymorphism, Genetic MeSH
- Publication type
- Review MeSH
Cíl studie: Cílem naší studie bylo prozkoumat možné asociace inzerčně/delečního angiotensin-konvertujícího enzymu (I/D ACE) polymorfismu s výskytem gestačního diabetu. Soubor a metodika: Do studie bylo zařazeno 53 zdravých těhotných žen a 48 žen s gestačním diabetem. Pacientky byly hospitalizovány na Gynekologicko-porodnické klinice MU Brno v období 10/2004 – 10/2005. Vždy se jednalo o spontánní jednočetnou graviditu. Odběr periferní krve, izolace DNA standardní technikou s použitím proteinázy K. Genotypy I/D ACE byly stanoveny prostřednictvím alelově specifických primerů. Výsledky: Neprokázali jsme statisticky signifikantní rozdíl v genotypových distribucích (Pg) Pg = 0,115 ani v alelických frekvencích (Pa) Pa = 0,873 mezi zdravými matkami a pacientkami s gestačním diabetem. U žen se dvěma a více porody v anamnéze jsme prokázali signifikantní rozdíl v distribuci genotypů (Pg=0,03); hraničně signifikantní rozdíl v distribuci genotypů jsme také nalezli u žen s 1 a více potraty v anamnéze (Pg=0,08). Závěr: Podle našich výsledku lze variabilitu v genu pro ACE považovat za jeden z faktorů, jež přispívají k manifestaci gestačního diabetu, I/D ACE polymorfismus však nelze na základě našich dat považovat za genetický marker gestačního diabetu.
Aim of the study: The aim of the study was to investigate possible associations of the Angiotensin – converting enzyme insertion/deletion (I/D ACE) polymorphism with gestational diabetes mellitus occurrence. Methods: Number of 53 healthy pregnant women (controls) and 48 women with gestational diabetes mellitus were included in the study. The woman patients were hospitalised in the Clinic of Obstetrics and Gynaecology, Masaryk University Affiliated hospital Brno during the period 10/2004 – 10/2005. In all cases there was the spontaneous one baby pregnancy. The procedure was obtaining the peripheral blood samples from women of those two groups and isolation of their DNA using standard technique with the use of proteinase K. I/D ACE genotype of each person was determined using allele specific primers. Results: We did not prove significant association neither of the genotype distribution (Pg) Pg = 0.115 nor allele frequency (Pa) Pa = 0.873 between controls and women with gestational diabetes mellitus. The significant differences of genotype distributions (Pg=0.03) were observed in women with two and more labours in anamnesis. Borderline significant differences of genotype distributions (Pg=0.08) were found in women with one and more abortions in anamnesis. Conclusions: According to our results the variability in ACE gene can be taken as factor contributing to manifestation of gestational diabetes mellitus. According to results of our study I/D ACE polymorphism can’t be taken as genetic marker of gestational diabetes mellitus.
- MeSH
- Angiotensins analysis diagnostic use genetics MeSH
- Diabetes, Gestational diagnosis etiology physiopathology MeSH
- Pregnancy Complications etiology metabolism physiopathology MeSH
- Humans MeSH
- Molecular Biology methods MeSH
- Polymorphism, Genetic genetics MeSH
- Renin-Angiotensin System genetics MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Comparative Study MeSH
Insertion-deletion polymorphisms (INDELs) are diallelic markers derived from a single mutation event. Their low mutation frequency makes them suitable for forensic and parentage testing. The examination of INDELs thus combines advantages of both short tandem repeats (STR) and single nucleotide polymorphisms (SNP). This type of polymorphisms may be examined using as small amplicon size as SNP (about 100 bp) but could be analyzed by techniques used for routine STR analysis. For our population study, we genotyped 55 unrelated Czech individuals. We also genotyped 11 trios to analyze DIPplex Kit (QIAGEN, Germany) suitability for parentage testing. DIPplex Kit contains 30 diallelic autosomal markers. INDELs in DIPplex Kit were tested with linkage disequilibrium test, which showed that they could be treated as independent markers. All 30 loci fulfill Hardy-Weinberg equilibrium. There were several significant differences between Czech and African populations, but no significant ones within European population. Probability of a match in the Czech population was 1 in 6.8 × 10(12); combined power of discrimination was 99.9999999999%. Average paternity index was 1.13-1.77 for each locus; combined paternity index reached about 27,000 for a set of 30 loci. We can conclude that DIPplex kit is useful as an additional panel of markers in paternity cases when mutations in STR polymorphisms are present. For application on degraded or inhibited samples, further optimization of buffer and primer concentrations is needed.
- MeSH
- Sex Determination Analysis methods MeSH
- DNA Fingerprinting methods MeSH
- Gene Frequency MeSH
- Genotype MeSH
- Humans MeSH
- Microsatellite Repeats MeSH
- Multiplex Polymerase Chain Reaction MeSH
- INDEL Mutation * MeSH
- Paternity * MeSH
- Polymorphism, Genetic * MeSH
- Genetics, Population * MeSH
- Racial Groups genetics MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND: We evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI). METHODS: A total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI. RESULTS: In comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥ 55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]). CONCLUSIONS: These results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.
- MeSH
- Acute Disease MeSH
- Peptidyl-Dipeptidase A genetics physiology MeSH
- Angioplasty, Balloon, Coronary MeSH
- Gene Deletion MeSH
- Ventricular Dysfunction, Left etiology genetics MeSH
- Myocardial Infarction complications therapy MeSH
- Mutagenesis, Insertional MeSH
- Humans MeSH
- Polymorphism, Genetic MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Cholesterol blood MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- Blood Pressure MeSH
- Humans MeSH
- Polymerase Chain Reaction MeSH
- Polymorphism, Genetic MeSH
- Genetics, Population MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
