Polymorphism of Interleukin 1B May Modulate the Risk of Ischemic Stroke in Polish Patients.

Background and Objectives: Inflammation plays a crucial role in the pathophysiology of ischemic stroke (IS). Interleukin-1B and interleukin-1 receptor antagonists are key factors in inflammatory processes. Aims: The aims of our study were to evaluate the relationship between genetic variation in interleukin-1B (IL1B) rs1143627 and interleukin-1 receptor antagonist (IL1RN) variable-number-tandem-repeats (VNTR), and overall IS and subtype prevalence rates. Materials and Methods: The analysis included 147 hospitalized Polish patients with IS diagnosed using conventional criteria. The control group consisted of 119 healthy subjects. Genotypes were determined by polymerase chain reaction. Results: A significant association between rs1143627 and stroke was found. The -31C IL1B polymorphism showed an association with overall IS, OR = 2.30 (1.36-3.87) p = 0.020. An association was also detected for LVI (large vessel infarction) subtypes of stroke. After risk factor adjustment (age, diabetes mellitus, dyslipidemia), the C allele was found to be an independent risk factor for LVI, OR = 1.99 (1.05-3.79) p = 0.036. Significant association was not observed between IL1RN alleles and IS. Conclusions: Our results suggest that the C allele of IL1B rs1143627 may be associated with susceptibility to overall IS and LVI subtypes of stroke in the Polish population.

Association of BMPR1A polymorphism, but not BMP4, with kidney size in full-term newborns.

BACKGROUND: A correlation between renal mass and nephron number in newborns allows the use of total kidney volume at birth as a surrogate for congenital nephron number. As the bone morphogenetic protein type 4 (BMP4), and its receptor type 1A (BMPR1A, ALK3), play an important role in renal development, we hypothesized that common, functional polymorphisms in their genes might be responsible for variation in kidney size among healthy individuals. METHODS: We recruited 179 healthy full-term newborns born to healthy women. Kidney volume was measured sonographically. Total kidney volume (TKV) was calculated as the sum of left and right kidneys, and normalized for body surface area (TKV/BSA). Genomic DNA was extracted from umbilical cord blood leukocytes, and c.455T > C (rs17563) BMP4 and c.67 + 5659A > T (rs7922846) BMPR1A genotypes were identified by PCR-RFLP. RESULTS: TKV/BSA in newborns carrying at least one A BMPR1A allele (AA + AT) was significantly reduced by approximately 13 % as compared with TT homozygous newborns (106.7 ± 21.5 ml/m(2) vs. 122.7 ± 43.8 ml/m(2), p < 0.02). No significant differences in TKV/BSA were found among newborns with different BMP4 genotypes. CONCLUSIONS: Results suggest that rs7922846 BMPR1A polymorphism may account for subtle variation in kidney size at birth, reflecting congenital nephron endowment.

Association of the rs3039851 Insertion/Deletion in the Gene PPP3R1, Which Encodes the Regulatory Calcineurin Subunit B Type 1, with Left Ventricular Mass in Polish Full-Term Newborns.

BACKGROUND: The five base-pair (bp) insertion/deletion (rs3039851) polymorphism in the PPP3R1 gene, which encodes calcineurin subunit B type 1, has been found to be associated with left ventricular hypertrophy (LVH) in hypertensive patients and in athletes. The aim of this study is to analyze the possible association between PPP3R1:rs3039851 polymorphism and left ventricular mass (LVM) in full-term healthy newborns. METHODS: The study group consisted of 162 consecutive, full-term, healthy newborns. Two-dimensional M-mode echocardiography was used to assess LVM. The PPP3R1:rs3039851 polymorphism was identified by PCR-RFLP in genomic DNA extracted from cord blood leukocytes. RESULTS: No significant differences were found between newborns homozygous for the reference allele (5I/5I, n = 135) and newborns carrying at least one 5D allele (n = 27) for LVM standardized for body mass, body length or body surface area (LVM/BM, LVM/BL or LVM/BSA, respectively). However, the frequency of PPP3R1:rs3039851 genotypes with a 5D allele (5I/5D + 5D/5D) among newborns with the largest LVM/BM or LVM/BSA (upper tertile) was statistically significantly higher compared with the prevalence in individuals with the lowest values of both indices (lower tertile). CONCLUSIONS: Our results suggest that the PPP3R1:rs3039851 polymorphism may contribute to subtle variation in left ventricular mass at birth.

Analysis of Genetic Variants in the Glucocorticoid Receptor Gene NR3C1 and Stenosis of the Carotid Artery in a Polish Population with Coronary Artery Disease.

Background: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Early diagnosis and elimination of risk factors are crucial for better managing CVDs. Atherosclerosis, whose development might be associated with glucocorticoids (GCs), is a critical factor in the development of carotid artery (CA) stenosis and most other CVDs. Aim: To investigate the association of Tth111I, N363S, and ER22/23EK-NR3C1 polymorphisms and the incidence of CA stenosis. Methods: The study group consisted of 117 patients diagnosed with coronary artery disease (CAD) and CA stenosis and 88 patients with CAD and ruled out CA stenosis. Genomic DNA was extracted from blood, and genotyping was carried out using Tth111I, N363S, and ER22/23EK-NR3C1 polymorphism sequencing. Results: No significant association between studied polymorphisms and the incidence or the severity of CA stenosis in the Polish population with CAD was found. Conclusion: This is the first study that proves that common NR3C1 gene variants do not influence CA stenosis and probably are not associated with atherosclerosis. The search for genes that can act as prognostic markers in predicting CA stenosis is still ongoing.

Efficacy of AutoPulse for Mechanical Chest Compression in Patients with Shock-Resistant Ventricular Fibrillation.

INTRODUCTION: Sudden cardiac arrest is one of the most common causes of death. In cases of shock-resistant ventricular fibrillation, immediate transport of patients to the hospital is essential and made possible with use of devices for mechanical chest compression. OBJECTIVES: The efficacy of AutoPulse in patients with shock-resistant ventricular fibrillation was studied. METHODS: This is a multicentre observational study on a population of 480,000, with 192 reported cases of out-of-hospital cardiac arrest. The study included patients with shock-resistant ventricular fibrillation defined as cardiac arrest secondary to ventricular fibrillation requiring ≥3 consecutive shocks. Eventually, 18 patients met the study criteria. RESULTS: The mean duration of resuscitation was 48.4±43 min, 55% of patients were handed over to the laboratory while still in cardiac arrest, 83.3% of them underwent angiography and, in 93.3% of them, infarction was confirmed. Coronary intervention was continued during mechanical resuscitation in 50.0% of patients, 60% of patients survived the procedure, and 27.8% of the patients survived. CONCLUSIONS: Resistant ventricular fibrillation suggests high likelihood of a coronary component to the cardiac arrest. AutoPulse is helpful in conducting resuscitation, allowing the time to arrival at hospital to be reduced.

The Genetic Variants in the Renin-Angiotensin System and the Risk of Heart Failure in Polish Patients.

(1) Background: Heart failure (HF) is a complex disease and one of the major causes of morbidity and mortality in the world. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF. (2) Aim: To investigate the association of RAS key genetic variants, rs5051 (A-6G) in the gene encoding angiotensinogen (AGT), rs4646994 (I/D) in the gene for angiotensin I converting enzyme (ACE), and rs5186 (A1166C) in the gene encoding type 1 receptor for angiotensin II (AGTR1), with the HF risk in the cohort of Polish patients. (3) Methods: The study group consisted of 415 patients that were diagnosed with HF, while the control group comprised of 152 healthy individuals. Genomic DNA were extracted from blood and genotyping was carried out using either PCR or PCR-RFLP for ACE or AGT and AGTR1 variants, respectively. (4) Results: No association has been found between the I/D ACE and heart failure. The HF risk was significantly higher for AG AGT heterozygotes (overdominance: AG versus AA + GG) and for carriers of the G AGT allele in codominant and dominant modes of inheritance. However, the risk of HF was significantly lower in the carriers of at least one C AGTR1 allele (AC or CC genotypes) or in AC AGTR1 heterozygotes (overdominant mode). There was a significant relationship for AGT and HF patients in NYHA Class I-II for whom the risk was higher for the carriers of the G allele, and for the AG heterozygotes. There was also a significant interaction between heterozygote advantage of AGT and BMI increasing the risk for HF. (5) Conclusion: Our results suggest that the A(-6)G AGT polymorphism may be associated with HF in the Polish population and the HF risk seems to be modulated by the A1166C AGTR1 polymorphism.

Low frequency haplotypes of E-selectin polymorphisms G2692A and C1901T give increased protection from coronary artery disease.

BACKGROUND: E-selectin polymorphisms are an independent atherosclerosis and coronary artery disease (CAD) risk factor. This study aimed to investigate the link between the C1901T and G2692A E-selectin tagging SNPs and their haplotypes and the extent of coronary artery disease in Polish patients. MATERIAL/METHODS: For this study 321 patients were recruited CAD extent by coronary angiography and E selectin gene variant were investigated using HapMap, PCR/RFLP, multivariate logistic regression and haplotype analysis. RESULTS: Frequency distributions of the C1901T and G2692A polymorphisms were significantly different in CAD patients as compared to control subjects (p=0.037 and p=0.025, respectively). The C1901T polymorphism was found to be an independent genetic predictor of risk of CAD (OR=3.01) in a multivariate model adjusted for classic, environmental risk factors. The A-C and G-T haplotypes showed the strongest significant associations with CAD. The A-C haplotype proved to be significantly more common in controls (haplotype frequency 9.2%) than in CAD (5.7%, p=0.048); the G-T haplotype was not found among control subjects (0.0%) but was found in CAD (1.3%, p=0.0099). CONCLUSIONS: Associations between the C1901T and G2692A E-selectin polymorphisms and CAD in the Polish population were found. Investigated variants correlated with the risk of coronary artery disease development but not with the extent of coronary artery vascular changes. In the haplotype analysis, 2 haplotypes influenced CAD--the A-C haplotype (7%) proved to exert a protective effect against CAD, while the effect of the less frequent G-T haplotype (1%) was associated with significant increase in CAD risk.

Concentrations of Mg, Ca, Fe, Cu, Zn, P and anthropometric and biochemical parameters in adults with chronic heart failure.

BACKGROUND: The study investigated the relationship between the concentrations of Mg, Ca, Fe, Cu, Zn, P and anthropometric and biochemical parameters in the blood serum of patients with heart failure (HF) and the potential influence on the development and progression of HF. MATERIAL & METHODS: The study included 214 patients (155 men and 59 women), aged 40-87 years, presenting symptoms or signs typical of HF (according to the NYHA functional classification). Serum concentrations were determined for Mg, Ca, Fe, Cu, Zn, P, C-reactive protein (CRP), creatinine, urea, triglyceride levels (TG), total cholesterol (CH), high density protein (HDL), low density protein (LDL). The levels of macro-and microminerals were analysed using inductively coupled serum optical emission spectrometry (ICP-OES). RESULTS: Our study confirmed the role of known risk factors in the development of heart failure, including: overweight, diabetes, hypertension, high triglycerides (TG), high total cholesterol (CH), high levels of low density protein (LDL) and reduced levels of high density protein (HDL), high CRP, high creatinine. Moreover, deficient serum concentrations of Mg (47% of the studied men and 54% of the women) and Cu (in 44% of men and more than 30% of women) were observed, as well as subnormal serum Fe (2% of women) and Zn (1% of men). Elevated serum Ca was found in 50% of men and 49% of women. In 44% of the studied men and 52% of the studied women, P levels in serum were also above-average. The study revealed a significant positive correlation between serum levels of Ca and Mg, and also Ca and Cu in women. In men, serum Cu was positively correlated with Mg and Ca concentrations. In patients from group 1 (NYHA I-II), Mg content was positively correlated with Ca and Cu. In this patient group, Ca was also positively associated with Cu content in serum. In group 2 (NYHA III-IV), serum Mg concentration was significantly positively correlated with that of Cu and Ca. CONCLUSIONS: Changes in the serum concentrations of macro-and microminerals may significantly affect the severity of HF in Polish patients.

Key genetic variants in the renin-angiotensin system and left ventricular mass in a cohort of Polish patients with heart failure.

BACKGROUND: Heart failure (HF) is a complex disease that is under the control of different physiological systems. Left ventricular mass (LVM) is a strong predictor of HF. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF and LVM. AIMS: The aim of this study is to examine the association between RAS genetic variants and HF and LVM in the cohort of Polish patients with HF. METHODS: The study included 401 patients with HF. Two-dimensional M-mode echocardiography was used to assess LVM. Genomic DNA was extracted from blood, and genotyping of the angiotensin-converting enzyme (ACE) (rs4646994), angiotensinogen (AGT) (rs5051), and angiotensin II receptor type 1 (AGTR1) (rs5186) polymorphisms was carried out using polymerase chain reaction (PCR). RESULTS: A significant association was found between HF and the genotypes of G(-6)A AGT, and the homozygotes AA of AGT were significantly less common in the HF vs control group. The results of this study did not confirm the relationship between AGT, ACE and AT1R genetic variants with LVM in Polish patients with HF. CONCLUSIONS: Our results suggested that AGT polymorphism may play a protective role in the development of HF.

Genetic Polymorphisms of MMP1, MMP9, COL1A1, and COL1A2 in Polish Patients with Thoracic Aortopathy.

BACKGROUND: The pathogenesis of thoracic aortopathy is complex, and much evidence suggests the influence of genetic factors. Some genes with polymorphisms are widely considered critical factors in the initiation and development of aortic aneurysm. The aim of our study was to analyze the association of genetic polymorphisms of MMP1 rs1799750 (c.-1607G>GG), MMP9 rs3918242 (c.-1562C>T), COL1A1 rs1800012 (c.1245G>T), and COL1A2 rs42524 (c.1645G>C) with predisposition to thoracic aortopathy in Polish patients and with clinical characteristics of these patients. METHODS: The study was carried out with 96 patients with thoracic aortopathy (47 patients with ascending aortic aneurysm and 49 patients with thoracic aortic dissection) and 61 control subjects without thoracic aortopathy. The MMP1, MMP9, COL1A1, and COL1A2 polymorphisms were determined by PCR-RFLP. RESULTS: No significant differences in the frequency distributions of MMP1, MMP9, COL1A1, and COL1A2 genotypes or alleles were found (1) between the control group and patients with ascending aortic aneurysm (AsAA), (2) between the control group and patients with thoracic aortic dissection (TAD), or (3) between AsAA and TAD patients. Multivariate logistic regression analysis revealed that MMP1 and MMP9 polymorphisms were associated with the degree of aortic valve regurgitation. CONCLUSION: The results of our study did not support associations between MMP1, MMP9, COL1A1, and COL1A2 genetic variants with the risk of thoracic artery disease in Polish patients. However, rs1799750 MMP1 and rs3918242 MMP9 seem to be associated with the degree of aortic regurgitation.

Two Functional TP53 Genetic Variants and Predisposition to Keloid Scarring in Caucasians.

INTRODUCTION: Keloid is defined as a benign proliferative scar that grows beyond the confines of the original insult to the skin, invading into adjacent normal tissue. The pathogenesis of keloid is complex, and many evidences suggest the influence of genetic factors, among them the polymorphisms of the TP53 gene encoding tumor protein p53. OBJECTIVE: To investigate the association of rs1042522 (c.215G>C, p.Arg72Pro) and rs17878362 (16-bp insertion/duplication in intron 3) variants, two most frequently analyzed TP53 functional polymorphisms and the risk of keloid in Polish patients. MATERIALS AND METHODS: The rs1042522 and rs17878362 polymorphisms were identified by sequencing genomic DNA extracted from peripheral blood leukocytes of 86 keloid patients and from cordial blood leukocytes of 100 newborn infants consisting control group. RESULTS: The rs1042522 and rs17878362 TP53 genotype distributions both in keloid patients and in the control group conformed to the expected Hardy-Weinberg equilibrium. No significant differences in the distribution of rs1042522 and rs17878362 TP53 alleles or genotypes have been found between keloid patients and newborn controls. There is tight, but not complete, linkage disequilibrium between rs1042522 and rs17878362 TP53 polymorphisms (D' = 0.667, r = 0.448, and p=0). No significant differences in the distribution of rs1042522 and rs17878362 TP53 haplotypes or diplotypes have been found between keloid patients and newborn controls. CONCLUSIONS: Our results suggest the lack of association of rs1042522 and rs17878362 TP53 polymorphisms and their haplotypes or diplotypes with the susceptibility to keloid scarring in Polish patients.

E-selectin gene haplotypes are associated with the risk of myocardial infarction.

INTRODUCTION: Endothelial dysfunction is one of the most important factors implicated in the pathogenesis of coronary artery disease (CAD). The aim of this study was to investigate the association of the E-selectin gene (SELE) with CAD and CAD-related traits using tagging polymorphisms. MATERIAL AND METHODS: A total of 379 Polish patients who had undergone angiography were included: 261 patients with angiographically documented CAD, 202 CAD patients without myocardial infarction (CAD/MI(-) group) and 59 patients with myocardial infarction (CAD/MI(+) group) as well as 118 healthy control subjects (non-CAD). Eight tagging single nucleotide polymorphisms (SNPs) in the SELE gene were selected using genotype data from HapMap. Genotyping was performed using PCR-RFLP and PCR-DHPLC methods. RESULTS: The most common SELE haplotype in this analysis ([C;G;T;C;G;T], 31.2%) showed a negative association with myocardial infarction (MI) (CAD/MI(+) vs. non-CAD) under the additive (p = 0.001), dominant (p = 0.006) and recessive (p = 0.012) model. Two other haplotypes ([C;G;C;C;A;C], [C;A;C;A;G;T], 5.73% and 18.1%, respectively) were also negatively associated with MI under the additive and dominant model. We also found two haplotypes ([T;G;T;C;G;T], [C;G;C;C;A;T], 1.52% and 6.71%, respectively) associated with the risk for MI (CAD/MI(+) vs. CAD/MI(-)), acting in both additive (p = 0.04, p = 0.007, respectively) and dominant (p = 0.04, p = 0.004, respectively) manner. There was no association with either CAD/MI(-) or with severity of CAD expressed as the number of vessels involved. CONCLUSIONS: Our results suggest that SELE is one of the independent genetic factors modifying the risk of myocardial infarction.

Lipid derivatives of arachidonic acid used as markers of atherosclerotic plaque instability: a pilot study.

BACKGROUND: To compare the results of computer estimation of atherosclerotic plaque with biochemical data and ascertain any relationship with the occurrence of stroke. METHODS: The study involved 20 atherosclerotic plaques causing 70-99% stenosis of internal carotid arteries (ICA). Ultrasonographic examination (USG) images of plaques were analyzed using a computer program. A histogram was obtained for each plaque and a gray scale median (GSM) was determined for each histogram in order to measure the echogenicity of an examined plaque. Then the plaques, collected during endarterectomy, were examined with regard to the concentration of prostaglandins E2 (PGE2), thromboxane A2 (TXA2), and 8 - epi-prostaglandin F2α. This data was compared with GSM and the occurrence of stroke. RESULTS: The statistical analysis showed significant correlations between low GSM and the occurrence of strokes. Out of 10 plaques with GSM<35, 6 (60.0%) were associated with a stroke. In contrast, out of 10 plaques with GSM>35, only 1 (10.0%) had a stroke. In addition, there were significant differences in the plaque content of PGE 2, (P<0.05) and (TXA2, P<0.011) between groups. CONCLUSIONS: High levels of PGE2 and TXA2, correlated with the low GSM values, may be the features of unstable plaques and that may be associated with a risk for stroke.

[I/D polymorphism of angiotensin I converting enzyme gene and arterial hypertension in patients with type 2 diabetes mellitus]. / Polimorfizm I/D genu enzymu konwertujacego angiotensyne I a nadcisnienie tetnicze u chorych na cukrzyce typu 2.

UNLABELLED: Type 2 diabetes mellitus and arterial hypertension coexist very frequently. About 80% patients with type 2 diabetes suffer for hypertension, which is connected with higher morbidity and mortality from cardiovascular diseases. There are evidences that activation of the renin-angiotensin system (RAS), one of the most potent factors in blood pressure regulation, can decrease insulin sensitivity of tissues. As I/D polymorphism of angiotensin converting enzyme (ACE) gene can influence the activity of RAS, it may also influence both carbohydrate metabolism and blood pressure. AIM OF THE STUDY: To assess the relationship between the I/D polymorphism of ACE gene and frequency of hypertension and values of blood pressure in type 2 diabetic patients. MATERIAL AND METHODS: Examined group: 108 type 2 diabetic patients (38 women and 70 men), with mean duration of disease 9.07 +/- 6.68 years, mean age 59.98 +/- 9.10 years. We assessed following parameters: body mass index (BMI), waist/hip ratio (WHR), arterial blood pressure. Laboratory tests: concentration of the glucose, glycosylated hemoglobin (HbA1c), creatinine and urinary albumin excretion rate (UAER). Insulin resistance was calculated by the HOMA rate. I/D ACE gene polymorphism was evaluated by polymerase chain reaction (PCR). RESULTS: DD genotype carriers had significant higher systolic and diastolic blood pressure (147.8 +/- 19.8 vs 138.2 +/- 16.5 mm Hg, p = 0.03; 89.2 +/- 9.6 vs 81.7 +/- 8.6 mm Hg p = 0.004; respectively) than II patients. Groups with II, ID and DD genotype were not different in age, BMI, WHR, duration of diabetes, the prevalence and duration of arterial hypertension, degree of metabolic control of diabetes and insulin resistance assessed by HOMA rate. CONCLUSION: In type 2 diabetic patients the DD genotype of ACE gene is not connected with higher prevalence of hypertension, but it is associated with higher systolic and diastolic blood pressure.

[Relationship between I/D polymorphism of angiotensin I converting enzyme gene and microvascular complications in type 2 diabetic patients]. / Zaleznosc miedzy polimorfizmem I/D genu enzymu konwertujacego angiotensyne I a powiklaniami o typie mikroangiopatii u chorych na cukrzyce typu 2.

BACKGROUND: Type 2 diabetes mellitus is an increasing problem in developed countries. Microvascular diabetic complications can lead to worsening of the quality of life and lifespan shortening of diabetic patients. The renin-angiotensin system (RAS) seems to play an important role in microvascular blood flow. I/D polymorphism of angiotensin I converting enzyme (ACE) affecting activity of RAS may contribute to development of microvascular diabetic complications. AIM: The aim of the study was to evaluate association between I/D polymorphism of ACE gene and presence of microangiopathic complications in type 2 diabetic patients. MATERIAL AND METHODS: 108 type 2 diabetic patients (70 men and 38 women), mean age 60.0 +/- 9.1 years with mean duration of diabetes 9.1 +/- 6.7 years were assessed for presence of microvascular complications (nephropathy, retinopathy, peripheral neuropathy). Subjects were examined for metabolic control of diabetes, lipid profile and degree of insulin resistance based on HOMA rate. I/-D ACE gene polymorphism was evaluated using polymerase chain reaction (PCR). RESULTS: Diabetic nephropathy was diagnosed in 44 patients (42.7%), retinopathy in 34 patients (31.8%), and peripheral neuropathy in 58 patients (53.7%). Microvascular complications were found (at least one complication) in 83 patients (76.9%). Patients with microangiopathy and without microangiopathy were characterized by similar distribution of I/D ACE gene polymorphism. In carriers of DD ACE genotype blood pressure and HDL-cholesterol serum concentrations were higher than in patients with II polymorphism. CONCLUSIONS: 1. The ACE genotype is not associated with the presence of microvascular complications in type 2 diabetic patients. 2. In type 2 diabetic patients there is an association between DD genotype and higher blood pressure and serum HDL-cholesterol level.

Is there an association between angiotensin-converting enzyme gene polymorphism and functional activation of monocytes and macrophage in young patients with essential hypertension?

BACKGROUND: This study was undertaken to determine whether the phenotype of monocytes and monocyte-derived macrophages is more proatherogenic in young persons with arterial hypertension and whether this phenotype is affected by smoking or polymorphism of the angiotensin-converting enzyme (ACE) gene. METHODS: We enrolled 40 young patients (24.1 +/- 4.7 years) with previously untreated arterial hypertension and 40 age-matched healthy controls. There were 20 smokers and 20 non-smokers in each group. RESULTS: In the hypertensive group, we found enhanced monocyte expression of CD11a (P < 0.001), reduced expression of CD49d (P < 0.001) and CD62L (P < 0.005), greater oxidative stress in resting and phorbol-12-mistrate-13-acetate-stimulated monocytes (P < 0.001), enhanced adhesion of monocytes to endothelial cells (P < 0.001), greater expression of CD36 on monocyte-derived macrophages (P < 0.001), and enhanced production of reactive oxygen species by resting and phorbol-12-mistrate-13-acetate-stimulated macrophages (P < 0.001). Cigarette smoking by hypertensive patients was associated with enhanced (P < 0.002) CD11a expression. There were no associations of ACE gene polymorphism with cellular expression or reactive oxygen species production studied among hypertensive patients. Only CD62L expression in DD homozygote participants was higher (P < 0.039) than in II homozygote participants. CONCLUSIONS: It is concluded that arterial hypertension affects the function of monocytes/macrophages in young persons. Polymorphism of the ACE gene is without effect on the functional activation of monocytes and macrophages.

Insertion/deletion polymorphism of angiotensin I converting enzyme gene and left ventricular hypertrophy in patients with type 2 diabetes mellitus.

INTRODUCTION: Left ventricular hypertrophy (LVH) is a well known risk factor of death from cardiovascular causes. Patients with type 2 diabetes mellitus are at particularly high risk of developing cardiovascular disease, which accounts for 80% of deaths in this group. Type 2 diabetes mellitus is probably related to increased left ventricular mass (LVM). Existing data show that the renin-angiotensin-aldosterone (RAA) system may play a role in the development of LVH. Since the I/D polymorphism of angiotensin-converting enzyme (ACE) gene influences the activity of RAA, it is likely that it could also have an impact on LVH. AIM: To assess the relationship between I/D polymorphism of the ACE gene and the severity of LVH assessed by echocardiography (Echo) in patients with type 2 diabetes mellitus. METHODS: The study group consisted of 103 patients (37 women and 66 men; mean age 60.1+/-9.1 years) suffering from type 2 diabetes mellitus with a mean duration of 9.0+/-6.5 years. BMI, waist-to-hip ratio (WHR), arterial blood pressure, LVM and LVM index (LVM indexed for body surface area [g/m(2)] or height raised to the power 2.7 [g/m(2.7)]) were evaluated. I/D polymorphism of the ACE gene was determined using polymerase chain reaction (PCR). RESULTS: Distribution of I/D polymorphism of the ACE gene in the study group was as follows: genotype II--32.0%, ID--42.7%, DD--25.2% of patients. LVH was diagnosed in 43-71% of patients (depending on criteria used). Distribution of individual genotypes was similar in patients with and without LVH. Genotypes II, ID and DD were observed in 37.3%, 31.4% and 31.4% of patients without LVH (according to the Levy criteria) and in 26.9%, 53.9%, 19.2% in the LVH group, respectively. In persons with DD genotype, when compared to group II, significantly higher values of systolic and diastolic blood pressure were noted (147.7+/-20.2 vs 138.2+/-16.7 mmHg, p=0.03 and 89.4+/-9.7 vs 81.9+/-8.7 mmHg, p=0.004, respectively). CONCLUSIONS: In patients with type 2 diabetes mellitus there is no relationship between I/D polymorphism of the ACE gene and LVH.

[The assessment of the influence of natural coffee and its modified form on the level of homocysteine, vitamin B6 and folic acid in healthy volunteers]. / Ocena wplywu kawy naturalnej i jej formy zmodyfikowanej na stezenie homocysteiny oraz witaminy B6 i kwasu foliowego u zdrowych wolontariuszy.

UNLABELLED: The aim of our investigation was the assessment of the influence of natural coffee and that modified by water and pressure extraction (60% less of 2-methyl isoborneol) on the level of homocysteine, folic acid and vitamin B6 in healthy volunteers. MATERIAL AND METHODS: The study was conducted on 36 healthy volunteers. 20 women and 16 men; smokers constituted half of the group. The study was conducted as a double blind trial (coffee without labels) after randomization into two groups. Initially for 4 weeks, one group drank natural coffee and the other a modified one. After four weeks there was a 28-day break in drinking coffee, after which the groups swapped roles and another trial lasted for the subsequent 4 weeks. All people examined drank three servings of coffee a day brewed from 13 g of material in 180 ml of boiling water. Throughout the entire experiment the examined subjects did not change their diets and did not take any vitamin supplements. Blood for analysis was drawn four times and the following analyses were carried out. homocysteine, folic acid, vitamin B6 total, LDL and HDL-cholesterol, triglicerides, Lp(a) and fibrinogen. RESULTS: We found a significant increase level of plasma homocysteine from 9.6 to 11.4 micromol/l (p < 0.001) in persons drinking natural, unfiltered coffee. However drinking modified coffee free from irritants resulted in a tendency towards lowering the level of homocysteine (from 9.1 to 8.7 micromol/l). CONCLUSIONS: From the above study it may be concluded that lowering the content of irritants in coffee results in reducing its undesired influence on the homocysteine level. Reduction of natural coffee consumption or its change on coffee with lowering the content of irritants should be recommended to cardiovascular disease persons.

Association Between RET (rs1800860) and GFRA1 (rs45568534, rs8192663, rs181595401, rs7090693, and rs2694770) Variants and Kidney Size in Healthy Newborns.

BACKGROUND: Abnormal congenital nephron number has been implicated in the pathogenesis of hypertension and renal disease. The RET receptor complex propagates signals essential for nephrogenesis and the RET c.1296G>A polymorphism, leading to aberrant splicing of exon 7, is associated with reduced kidney volume, a surrogate for nephron endowment. The glial cell-derived neurotrophic factor (GDNF) family receptor alpha 1 (GFRA1) is a component of the RET receptor complex, and three alternatively spliced GFRA1 transcripts (with or without exon 5) have been identified. In rats, exclusion of exon 5 results in stronger GDNF binding affinity and RET activation. The aims of this study were to investigate further the relationship between RET c.1296G>A and kidney volume, and also to investigate the association between the GFRA1 polymorphisms near and within the alternatively spliced exon 5, as well as the functional 5'-UTR c.-193C>G with kidney volume. MATERIALS AND METHODS: The study included 188 healthy full-term newborns. Genotyping of the RET (NM_020975.4:c.1296G>A, rs1800860) and GFRA1 (NM_005264.5:c.-193C>G, rs45568534; c.419-87A>G, rs8192663; c.429G>A, rs181595401; c.433+127A>G, rs7090693; c.433+245A>G, rs2694770) polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism, minisequencing, or sequencing. Total kidney volume (TKV) was determined by ultrasound and normalized to body surface area (TKV/BSA). Both marker-by-marker and haplotype-based methods were used to test for associations between polymorphisms and TKV/BSA. RESULTS: TKV/BSA in RET c.1296A allele carriers was significantly lower compared with GG homozygotes (103 ± 23 vs. 110 ± 19 mL/m2, p = 0.034). c.429G>A was invariant in our sample. There was no association between any of the GFRA1 polymorphisms and renal volume. CONCLUSIONS: RET c.1296A may be a common susceptibility allele for nephron underdosing-related diseases. The 5'-UTR and intronic variants near exon 5 of GFRA1 are not associated with nephron endowment.

Association of genetic variation in the natriuretic peptide system and left ventricular mass and blood pressure in newborns.

BACKGROUND: The natriuretic peptides play a key role in the modulation of left ventricular mass (LVM) and blood pressure (BP). We hypothesised that NPPA (natriuretic peptide precursor A gene), NPPB (natriuretic peptide precursor B gene), and NPPC (natriuretic peptide precursor C gene) are candidate genes possibly involved in the development or modulation of LVM at early life. AIM: To assess the relationship between NPPA, NPPB, and NPPC gene polymorphisms with LVM and BP in newborns. METHODS: A total of 206 healthy newborns were studied by two-dimensional M-mode echocardiography. The polymorphisms NPPA rs5065, NPPB rs198389, and NPPC rs5268 were characterised. RESULTS: Newborns carrying the C allele of the NPPB polymorphism had significantly lower LVM/body surface area (BSA) and LVM/body weight (BW) values when compared with newborns' homozygotes for the T allele (41.76 g/m2 vs. 48.31 g/m2, p adjusted = 0.044 and 2.78 g/kg vs. 3.26 g/kg, p adjusted = 0.031, respectively). An association was observed between NPPA genotype and systolic BP, diastolic BP, and mean arterial pressure ≥ 90th percentile (p = 0.029, p = 0.0048, p = 0.004, respectively). Also an association was observed for systolic BP ≥ 90th percentile for NPPB (p = 0.016). CONCLUSIONS: The present study shows that the NPPB gene polymorphism is associated with modulation of LVM in newborns. The NPPA and NPPB gene polymorphisms are associated with BP.