Jan Máchal

Apolipoprotein E gene polymorphisms in relation to chronic periodontitis, periodontopathic bacteria, and lipid levels

OBJECTIVE Inflammatory periodontal diseases may be associated with common systemic conditions and, as recently described, alterations in lipid levels in the blood. The aim of this study was to determine the possible effects of apolipoprotein E (ApoE) genotypes on the lipid levels in healthy people and patients with chronic periodontitis (CP) in relation to periodontopathic bacteria. DESIGN This case-control study comprised 469 unrelated subjects. The genomic DNA of 294 patients with CP and 175 healthy/non-periodontitis controls were genotyped, using the real-time polymerase chain reaction (RT-PCR) method, for ApoE (rs429358 and rs7412) gene polymorphisms. Subgingival bacterial colonization was investigated by the DNA microarray using a periodontal pathogen detection kit and lipid levels were measured in a subgroup of subjects (N = 275). RESULTS There was no evidence for a significant association between ApoE gene polymorphisms and CP (P > 0.05). Patients with CP had increased levels of total cholesterol and low-density lipoprotein (LDL) compared to controls (P< 0.05); however, no significant difference was found for triglyceride and high-density lipoprotein (HDL) levels. ApoE gene variability influenced LDL levels marginally (P = 0.08) but it did not modify total cholesterol, triglyceride, and HDL levels or the occurrence of periodontal pathogens in subgingival pockets.(23) CONCLUSIONS: In the Czech population studied, ApoE genetic variations were not associated with susceptibility to CP or the presence of periodontopathic bacteria.

Patients with chronic three-vessel disease in a 15-year follow-up study: genetic and non-genetic predictors of survival.

AbstractGenetic and non-genetic predictors of 15-year survival in patients with chronic three-vessel disease (3VD) were investigated.Coronary angiography was performed on 810 subjects with symptoms of stable ischemic heart disease in 1998. The patients with 3VD were genotyped for 23 candidate polymorphisms covering the PPAR-RXR pathway, matrix metalloproteinase-2, renin–angiotensin–aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Fifteen-year survival data were obtained from the national insurance registry. All data were available in the case of 150 patients with 3VD. Statistical analysis used stepwise Cox regression with dominant, recessive, or additive mode of genetic expression. Involved variables included age, sex, BMI, blood pressure, diabetes, ejection fraction, left main stenosis, previously diagnosed coronary stenosis, myocardial infarction in personal history, and coronary bypass along with polymorphisms pre-selected by log-rank tests.Out of the 23 polymorphisms, four were included in the model construction. SNP in the IL-6 gene rs1800795 (−174 G/C) has been found to be a significant predictor of survival. This SNP was in a linkage disequilibrium with rs1800797 (−597 G/A) in the same gene (D′ = 1.0), which was also found to constitute a significant predictor of survival when rs1800795 was not included in the model construction. Age, increased BMI, diabetes, low EF, and left main stenosis were also significant predictors in all models.Age, increased BMI, diabetes, low ejection fraction, left main stenosis, and genetic variation in the IL-6 promoter were established as significant independent risk factors for the survival of patients with three-vessel disease.

Apolipoprotein E polymorphism is associated with both number of diseased vessels and extent of coronary artery disease in Czech patients with CAD

AIMS The impact of ApoE polymorphism on angiographic parameters was assessed in patients referred for coronary angiography. METHODS Elective coronary angiography was performed in 671 subjects (525 men, 146 women, mean age 60 ± 10 years) with symptoms of ischemic heart disease. The patients were divided into: no CAD group (smooth coronary vessels, n=83), one-vessel (n=155), two-vessel (n=170) and three-vessel disease (n=196). Patients with stenoses 0-50% were excluded. Within patients with CAD, we evaluated overall extent of CAD measured by the number of stenotic segments according to AHA (1 segment vs. 2-3 vs. ≥4), and the severity of the most serious stenosis (in percent). ApoE genotype was determined using real-time PCR. RESULTS The frequency of ε2/ε3 genotype (n=56) was lower in the three-vessel disease group compared to one-vessel disease (OR=0.25, P=0.0019), two-vessel disease (OR=0.31, P=0.0114) or no CAD group (OR=0.24, P=0.0057). Frequency of ε2/ε3 decreased with the number of affected segments (1 vs. ≥4: OR=0.35, P=0.0143). The ε3/ε4+ε4/ε4 genotypes (n=123) were more frequent in CAD patients altogether compared with no CAD group (OR=2.30, P=0.019), while no impact of the ε4 allele on angiographic parameters within the CAD patients was detected. In ε2/ε3 carriers with CAD, lower LDL-cholesterol, total cholesterol and lower use of lipid-lowering drugs were observed. CONCLUSIONS The results show predominantly focal form of CAD in patients with ε2/ε3 genotype. Lower LDL-cholesterol and total cholesterol may play the key role, although other contributing factors are discussed.

Comparison of maternal omentin-1 levels and genetic variability between spontaneous term and preterm births

Abstract Objective: To determine maternal omentin-1 levels and genetic variability in the omentin-1 gene in women with spontaneous term and preterm births (PTBs). Materials and methods: Maternal serum omentin-1 levels and the role of the omentin-1 Val109Asp (rs2274907) polymorphism were evaluated in 32 women with spontaneous term birth (sTB) and 30 women with spontaneous preterm birth (sPTB) including women with (n = 16) and without (n = 14) preterm premature rupture of membranes (PPROM). Results: Maternal omentin-1 levels were significantly lower in women with sPTBs compared to term births during the hospitalization period (p = .015). However, maternal omentin-1 levels were similar in women with sPTBs with and without PPROM (p = .990). Furthermore, the omentin-1 Val109Asp polymorphism was found to have no significant effect on omentin-1 serum levels. In addition, no significant differences in genotype distributions and allelic frequencies between sTB and sPTB were established. Conclusions: High omentin-1 levels in normal sTBs compared to PTBs without significant differences between cases with and without PPROM suggest that omentin-1 plays a potential role in the pathophysiology of PTB but not in the PPROM mechanism itself.

The Relation between eNOS -786 C/T, 4 a/b, MMP-13 rs640198 G/T, Eotaxin 426 C/T, -384 A/G, and 67 G/A Polymorphisms and Long-Term Outcome in Patients with Coronary Artery Disease.

Aim. The purpose of this study is to determine the association between eotaxin 426 C/T, −384 A/G, 67 G/A, eNOS −786 T/C, 4 a/b, and MMP-13 rs640198 G/T and prognosis of patients with known CAD. Methods. From total of 1161 patients referred to coronary angiography, 532 patients with angiographically confirmed CAD were selected. Their long-term outcome was followed up using hospital database. Subsequent events were assessed in this study: death or combined endpoint-myocardial infarction, unstable angina pectoris, revascularization, heart failure hospitalization, and cardioverter-defibrillator implantation. Results. The multivariate Cox regression model identified age, smoking, and 3-vessel disease as significant predictors of all-cause death. Further analysis showed that eotaxin 67 G/A (GA + AA versus GG) and eotaxin −384 A/G (GG versus GA + AA) were significant independent prognostic factors when added into the model: HR (95% CI) 2.81 (1.35–5.85), p = 0.006; HR (95% CI) 2.63 (1.19–5.83), p = 0.017; eotaxin −384 A/G was significantly associated with the event-free survival, but it did not provide the prognostic information above the effect of two- or three-vessel disease. Conclusion. The A allele in eotaxin 67 G/A polymorphism is associated with worse survival in CAD patients.

Eliminating the effect of pathomorphologically formed sperm on resulting gravidity using the intracytoplasmic sperm injection method

The aim of the present study was to test whether it is possible to eliminate a high percentage of morphologically abnormal sperm in male ejaculate by assisted reproduction using the intracytoplasmic sperm injection (ICSI) method. Treatment success was evaluated by comparing fertilization, clinical pregnancy and reproduction rates between males with heavy teratospermia (≤1% morphologically normal spermatozoa) and males with a higher percentage (>1%) of normal sperm. In total, 174 patients who had previously undergone 174 ICSI cycles (1 per each pair) were evaluated retrospectively. In the group of patients with heavily impaired sperm morphology (n=37), the percentage of normal spermatozoa was ≤1%. In the second group, males with >1% normal spermatozoa (n=137) were considered as patients with mildly impaired sperm morphology. The results of partner fertilization in these two groups were compared and a lower number of fertilized oocytes was identified in the patients with heavily impaired sperm morphology (P=0.038). However, neither the gravidity nor the take-home baby rates of the partners differed between the patients with mildly and heavily impaired sperm morphology. Trends opposite to that for fertilization were observed for gravidity and delivery [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.29–1.30; OR, 0.55; 95% CI, 0.26–1.24, respectively]. This indicates that the lower number of fertilized oocytes was not associated with the overall outcome of fertilization and that patients with heavily impaired sperm morphology experience the same benefit from ICSI as patients with mildly impaired sperm morphology.

Sleeping habits of adolescents in relation to their physical activity and exercise output: results from the ELSPAC study

Background Little is known about the effects of physical activity and fitness on sleep timing parameters in adolescence. Methods We investigated the development of sleep timing between age 8 and 15 and its association with physical fitness at age 15 in 787 adolescents (408 males, 379 females). Physical fitness was measured using the physical work capacity (PWC) protocol. Information on sport activity was collected at ages 11 and 15. Finally, the contribution of other covariates (sex, body mass index (BMI), parental education and occupational skill level) to the association between sleep parameters and physical fitness was evaluated. The correlation of BMI and physical fitness was assessed separately. Results Mild correlation of sleep duration at ages 8 and 15 was observed (r=0.08–0.16). Higher sport activity participation and physical fitness were found to be mildly associated with delayed bedtime and reduced sleep duration; the association with bedtime was significant after adjustment for all covariates. Sport activity at age 11 was not associated with sleep timing at age 15. Interestingly, higher BMI was linked to delayed bedtime and higher physical fitness. Conclusion Our findings do not support existing hypotheses suggesting the association of low physical activity and fitness with shorter sleep duration and high BMI in a generally non-obese adolescent population without severe sleep restriction.

Efficacy of P2Y12 receptor blockers after myocardial infarction and genetic variability of their metabolic pathways

BACKGROUND Various antiplatelet drugs are used following Acute Coronary Syndromes (ACS). Of them, adenosine diphosphate receptor P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor are currently used for post-ACS long-term treatment. Although they act on the same receptor, they differ in pharmacodynamics and pharmacokinetics. Several enzymes and transporters involved in the metabolism of P2Y12 inhibitors show genetic variability with functional impact. This includes Pglycoprotein, carboxylesterase 1 and, most notably, CYP2C19 that is important in clopidogrel activation. Common gain-of-function or loss-of-function alleles of CYP2C19 gene are associated with lower or higher platelet reactivity that may impact clinical outcomes of clopidogrel treatment. Prasugrel is considered to be less dependent on CYP2C19 variability as it is also metabolized by other CYP450 isoforms. Some studies, however, showed the relevance of CYP2C19 variants for platelet reactivity during prasugrel treatment as well. Ticagrelor is metabolized mainly by CYP3A4, which does not show functionally relevant genetic variability. Its concentrations may be modified by the variants of Pglycoprotein gene ABCB1. While no substantial difference between the clinical efficacy of prasugrel and ticagrelor has been documented, both of them have been shown to be superior to clopidogrel in post-ACS treatment. This can be partially explained by lower variability at each step of their metabolism. It is probable that factors influencing the pharmacokinetics of both drugs, including genetic factors, may predict the clinical efficacy of antiplatelet treatment in personalized medicine. CONCLUSION We summarize the pharmacokinetics and pharmacogenetics of P2Y12 inhibitors with respect to their clinical effects in post-myocardial infarction treatment.

The long-term effects of individual cardiac rehabilitation in patients with coronary artery disease

Uvod: Pozitivni vliv kardiorehabilitace byl opakovaně popsan a je dobře znam z hlediska kratko- a střednědobeho casoveho useku. Meně je znamo o dlouhodobých ucincich u pacientů s chronickou stabilni ischemickou chorobou srdecni.Cil: Cilem prace bylo vyhodnoceni dlouhodobeho ucinku individualni kardiorehabilitace u pacientů s ischemickou chorobou srdecni.Metodika: Sto padesat dva pacientů se stabilni ischemickou chorobou srdecni bylo retrospektivně rozděleno do dvou skupin podle dodržovani doporuceni stran individualni fyzicke aktivity, bez ohledu na absolvovani vedeneho treninku kardiorehabilitace. Skupina IT+, ktera provaděla individualni trenink podle doporuceni, byla srovnavana s pacienty, kteři toto odmitli (skupina IT-). Průměrna delka sledovani dosahovala 12,7 roku.Výsledky: Individualni trenink neměl žadný vliv na delku přežiti po upravě na dalsi faktory, ale multivariantni analýza ukazala významnou souvislost mezi výskytem kardialnich přihod, jako jsou infarkt myokardu, nestabilni angina pectoris, koronarni revaskularizace a hospitalizace pro srdecni selhani: HR (95 % CI) 0,51 (0,30-0,89); p = 0,017.Zavěr: Domaci kardiorehabilitace a pravidelna fyzicka aktivita významně snižuji dlouhodobou kardialni morbiditu u pacientů s chronickou ischemickou chorobou srdecni.

Increased age-adjusted hazard of death associated with a common single nucleotide polymorphism of the human RAD52 gene in a cardiovascular cohort

Aging may be characterized as the progressive increase of the risk of death caused by a decrease of almost all bodily functions. While a great number of model organism studies have established the role of DNA double strand breaks (DSBs) as one of the main causes of aging, few studies have examined whether common polymorphisms in human DSB repair genes influence aging and mortality. More importantly, to the best of our knowledge, no longitudinal study has thus far examined the link between polymorphisms in DSB repair and the risk of death. This longitudinal study thus analyses whether four common polymorphisms (rs2155209, rs7963551, rs17105278, rs2735383) in four selected DSB repair genes (MRE11A, RAD52, RAD51B, NBS1) influence the hazard of age-adjusted death in a cohort of patients with typical symptoms of ischemic heart disease. The results have shown that rs7963551 G/T heterozygotes exhibit a significantly increased hazard of death when compared with the combined GG and TT homozygotes (HR=1.42, 95% CI: 1.06-1.91, p=0.018). This study indicates that the SNP affecting efficiency of DSB repair may influence aging in humans.