An association of ABCG8: rs11887534 polymorphism and HDL-cholesterol response to statin treatment in the Polish population.

BACKGROUND: Variation in lipid changes in response to statin treatment is associated with genetic polymorphism. Sterolin-1, encoded by ABCG5, and sterolin-2, encoded by ABCG8, together form a sterol transporter. There are some reports indicating association of rs11887534 (ABCG8:c.55G > C) polymorphism with lipid concentrations, both prior to and after statin treatment. The aim of this study was to analyze both baseline plasma lipids and their concentrations in response to statin treatment with regard to ABCG8: rs11887534 polymorphism in Caucasian patients of Polish origin. METHODS: The study group consisted of 170 consecutive adult out-patients treated with atorvastatin or simvastatin for a minimum of 2 months. Concentrations of triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) were measured before and after statin treatment. The ABCG8 polymorphism was identified by mini-sequencing genomic DNA extracted from peripheral blood leukocytes. RESULTS: There were no significant differences in regard to ABCG8 variants for baseline TG, TC, LDL-C and HDL-C as well as for TG, TC or LDL-C concentrations after statin treatment. However, patients carrying at least one C allele showed a decrease in post-statin HDL-C concentrations and the absolute and relative changes between post- and pre-statin HDL-C concentrations were negative in contrast to positive values in wild-type homozygotes. CONCLUSIONS: Our results suggest that the c.55C allele of the ABCG8: rs11887534 polymorphism might be associated with decrease in HDL-cholesterol in response to statin treatment in Polish patients.

BICD1 and Chromosome 18 Polymorphisms Associated With Recipients' Telomere Length Affect Kidney Allograft Function After Transplantation.

BACKGROUND: Reports regarding recipient's nonmodifiable genetic factors affecting telomerase activity and thus allograft function are lacking. Therefore the aim of this study was to analyze the associations between recipients' rs2735940 hTERT, rs2630578 BICD1, and rs7235755 chromosome 18 polymorphisms and kidney function after transplantation. METHODS: The study enrolled 119 white Polish kidney allograft recipients (64 men, 55 women; overall mean age, 47.3 ± 14.0 y). To identify genotypes of the studied polymorphisms, real-time polymerase chain reaction was performed. RESULTS: There were statistically significant differences in distribution of rs7235755 chromosome 18 polymorphism genotypes and alleles between recipients with delayed graft function (DGF) and without DGF (P = .03). The presence of A allele was significantly associated with higher risk of DGF occurrence (AA + GA vs GG: OR, 3.25 [95% CI, 1.16-9.14]; P = .02; GA vs GG: OR, 4.00 [1.35-11.82]; P = .01). Analysis of the rs2630578 BICD1 gene polymorphism genotypes revealed statistically significant differences in long-term creatinine concentrations. The presence of C allele of this polymorphism was significantly associated with higher creatinine concentrations 24, 36, and 18-48 months after transplantation (GC + CC vs GG: P = .008, P = .008, and P = .01, respectively). CONCLUSIONS: Recipients' polymorphisms of genes associated with telomere length, BICD1 and chromosome 18, but not hTERT, affect kidney allograft early and long-term function after transplantation. There is an urgent need for explanation of these observations in genome-wide association studies.

Prevalence and Clinical Outcome of CYP21A2 Gene Mutations in Patients with Nonfunctional Adrenal Incidentalomas.

Adrenal tumors, discovered incidentally in approximately 4.5% of imaging procedures, are known as adrenal incidentalomas. Nonclassic congenital adrenal hyperplasia, mild form of 21-hydroxylase deficiency, may lead to the development of adrenocortical tumors. The aim of the study was to evaluate prevalence of the most common nonclassic mutations of CYP21A2 gene in patients with adrenal incidentalomas and investigate possible relationship with clinical outcome. One hundred adult patients with such lesions were enrolled. Clinical, imaging and biochemical evaluation were performed to rule out hormonal overproduction or potential malignancy. All subjects and a control group of 100 neonates were genotyped for P30L, P453S, and V281L mutations of CYP21A2 gene using direct sequencing. Clinical and imaging features as well as hormone levels were analyzed. Heterozygous CYP21A2 gene mutations were detected in 8 subjects but not in the neonates. Thus, the risk of carrying mutant allele was significantly higher in subjects with adrenal tumors (OR=8.7; 95% CI=2.23-389.56; p=0.003). Mean concentrations of renin, basal, and stimulated 17-hydroxyprogesterone were higher and ACTH was lower in the carriers than in the remaining subjects. Furthermore, the carriers had higher incidence of hypertension (100 vs. 52.1%, p=0.008) and diabetes (50 vs. 11.9%, p=0.003). ACTH-stimulated 17-hydroxyprogesterone levels varied widely among the carriers. In summary, prevalence of P30L, P453S, and V281L mutations of CYP21A2 gene is increased in patients with adrenocortical tumors. In these subjects, carrying the analyzed mutant alleles may increase the risk of diabetes and hypertension. ACTH-stimulation test does not satisfactorily predict presence of heterozygous CYP21A2 mutations in patients with adrenal tumors.

Mapping of polar fox renal cortex proteins using two-dimensional gel electrophoresis and mass spectrometry--a preliminary study.

The aim of the present study was to establish protein map of polar fox (Alopex lagopus) renal cortex. Kidney cortex proteins of isoelectric point ranging from 3 to 10 were analysed using two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Sixteen protein spots corresponding to thirteen different gene products were identified. These proteins were divided into following groups: lipid and fatty acid metabolism, amino acid metabolism, energetic pathways, regulatory proteins, transport proteins and structural proteins. This is the first attempt to create reproducible 2-D map, of renal cortex proteins characteristic for polar foxes, used as animal model for carnivores. It is worth emphasizing that the results of this study may broaden currently available protein databases.

Immunohistochemical identification of aquaporin 2 in the kidneys of young beef cattle.

Aquaporin 2 (AQP2) is a small, integral tetrameric plasma membrane protein that is expressed in mammalian kidneys. The specific constitution of this protein and its selective permeability to water means that AQP2 plays an important role in hypertonic urine production. Immunolocalization of AQP2 has been studied in humans, monkeys, sheep, dogs, rabbits, rats, mice and adult cattle. We analyzed the expression of AQP2 in kidneys of 7-month-old Polish-Friesian var. black and white male calves. AQP2 was localized in the principal cells of collecting ducts in medullary rays penetrating the renal cortex and in the collecting ducts of renal medulla. AQP2 was expressed most strongly in the apical plasma membrane, but expression was observed also in the intracellular vesicles and basolateral plasma membrane. Our study provides new information concerning the immunolocalization of AQP2 in calf kidneys.

ß2-adrenergic receptor gene polymorphism and response to bronchodilating treatment evaluated by spirometry.

ß2-adrenergic receptors re abundantly expressed in airways, which explains the role of ß2 agonists, the strongest bronchodilators, in treatment of bronchial constriction. There may be a relation between ß2ADR gene polymorphism and the response to treatment with ß2 agonists. In the present study we attempted to study these relationship in vivo, estimating spirometric values before and after the use of salbutamol in reference to variant of ß2ADR gene polymorphisms. The study involved 148 healthy male volunteers. After the examination of the gene polymorphism of the ß2-adrenergic receptor (ß2-ADR) at nucleotide positions 46 and 79 (g.46 and g.79) we performed spirometry testing in all subjects. The pulmonary function was checked twice a day; before and 15 min after the administration of salbutamol. All subjects had normal basic values of spirometry. The use of salbutamol significantly increased spirometric values in all groups determined by ß2ADR gene polymorphisms. Analysis of the spirometric values in individual groups showed a significant increase only in peak expiratory flow (g.46AA and g.79CC). The results of this study give an insight into a possibly important mechanism of the response to treatment with ß2-agonists.

Estimation of BDNF gene polymorphism and predisposition to dependence development for selected psychoactive compounds: genetic aspects of addiction with the selected drugs, amphetamine, tetrahydrocannabinol and opiates.

The etiology of drug addiction, a central nervous system (CNS) disease, is not fully known. This complex problem is believed to be connected with concurrently affecting genetic, psychological and environmental factors. The development of addiction is connected with CNS reinforcement system and dopaminergic neurotransmission. Molecular processes are postulated to be of universal character and allow to presume a similar mechanism of dependence for both ethanol and other substances. Therefore, elements of dopaminergic transmission become excellent candidates for the examination of genetic influence on the development of addiction. A relationship between alcoholic disease and the presence of TaqIA1 and DRD2 alleles permits to initiate another investigation of gene-coding DRD2 dopamine receptor. The latest results indicate the importance of brain-derived neurotrophic factor (BDNF) in the regulation of dopaminergic route. The purpose of this research was to reveal the relationship between the Val66Met BDNF gene polymorphism and dependence of psychoactive agent. The examinations were performed with the Local Research Ethics Committee approval and patient's consent. The study group consisted of 100 patients (88 men and 12 women) aged 18-52 years, qualified for research program according to the International Classification of Diseases, Tenth Revision (ICD-10) requirements, medical examination and detailed questionnaire.

Frequencies of functional caspase 12 genotypes in the North Africa population.

Caspase 12(Csp-12) is a cysteine protease that plays a role in regulation of cytokine maturation. It is present either in a functional full-length variant (Csp-12L) that predisposes to a lower immune response or in an inactive, common version (Csp-12S) that contains a stop codon that results in a truncated form. Genomic DNA from unrelated North Africans, residents of 4th Nile Cataract Region in Sudan, was analyzed. One hundred umbilical blood samples of Polish newborns served as a reference group from the Caucasian population. The analysis of stop-codon polymorphism performed on the 212 human samples from Northern Sudan identified 6.6% individuals with heterozygous genotypes while not one homozygous Csp-12L was found. All examined Polish individuals were homozygous Csp-12S.

Possible counter effect in newborns of 1936A>G (I646V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10.

OBJECTIVE: Cyclic adenosine monophosphate/protein kinase A (PKA) is important in embryonic development. The human AKAP10 gene is polymorphic: 1936A>G results in changes to a PKA-binding domain and increased targeting to mitochondria. Previous studies found G1936 as 'deleterious' in adults, and this study investigates whether this holds true in preterm birth. STUDY DESIGN: Study group consisted of 80 preterm newborns (PTNs) born before the 38th gestation week. Control group consisted of 123 full-term healthy newborns born after the 37th gestation week with uncomplicated pregnancies. Genomic DNA was extracted from umbilical blood and AKAP10 genotypes were identified by PCR/restriction enzyme. RESULT: Significant differences in frequencies of 1936A>G genotypes/alleles between both groups were found. PTNs had increased frequency (55%) of AA homozygotes (odds ratio, AA versus AG+GG: 2.63 (95% confidence interval: 1.33 to 5.20), P=0.006) after adjustments: mothers with previous PTNs, smoking, first pregnancy, first delivery and Cesarean section. CONCLUSION: Results suggest G1936 is preventative factor against preterm birth, in contrast with previously asserted negative effects in adults.

The effect of cause of cadaveric kidney donors death on fibrinolysis and blood coagulation processes.

BACKGROUND: Organ donors can be generally divided into two groups according to the cause of their death. The first group is composed of those who died because of physical injuries, especially road traffic injury, and the second group, those who died from central nervous system (CNS) stroke or bleeding. The aim of our work was to examine hemostatic processes among kidney donors. MATERIALS AND METHODS: The 38 deceased kidney donors (KD) included 11 women and 27 men of overall average age of 37±12 years. The donor group of according to the cause of death, included 14 injured donors (ID) (41%) and 24 noninjured donors (ND) donors (59%). The control group consisted of 25 healthy volunteers matched for sex and age. We determined the following concentrations: antithrombin (AT), thrombin/antithrombin complexes (TAT), and prothrombin F1+2 fragments. The fibrinolytic parameter concentrations were: plasminogen (PL), plasmin/antiplasmin complexes (PAP), and D-dimers. RESULTS: Deceased kidney donors showed an increased plasma concentrations of TAT complexes (P<.000001) and prothrombin fragments F1+2 (P<.0000001); however, the protein C concentration was decreased (P<.000001). The antithrombin activity was similar to the control group. The concentrations of PAP complexes and d-dimers were higher (both P<.000001), but the level of PL lower among KD compared with controls (P<.0000001). The higher of TAT, PAP complexes, d-dimers, and F1+2 concentrations as well and as lower plasminogen and PC concentrations were evidence for increased activation of blood coagulation and fibrinolysis in cadaveric KD. However, analysis compairing ID versus ND donors revealed increased concentrations of PAP complexes (P<.05) and decreased amounts of TAT complexes (P<.01) among ID subgroup. The positive predictive value (PPV) and negative (NPV) for PAP complexes were 75% and 68% and for TAT, 71% and 57%, respectively. On the basis of these observations, we concluded that an intensive activation of fibrinolytic process occurs among the ID. In contrast, ND show intensive activation of blood coagulation.

Donor-recipient gender mismatch affects early graft loss after kidney transplantation.

BACKGROUND: We sought to determine the risk factors influencing the occurrence of early graft loss among kidney transplant recipients. STUDY DESIGN: One hundred forty-six potential donors and 230 kidney recipients were included in the study. Prior to organ procurement we collected demographic data as well as hemodynamic data of mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, systemic vascular resistance index acquired by means of a thermodilution method. The recipient data included age, gender, prior hemodialysis period, panel-reactive antibodies, cold ischemia time, renal insufficiency cause, and donor-recipient gender mismatch. We assessed the influence of the data on graft loss at 30 days after renal transplantation. To confirm the relationships, we performed statistical analyses using chi-square, Fisher exact, and V. Cramer tests. RESULTS: There were no significant relationships between the analyzed parameters and early graft loss in the study group except for gender mismatch. The 71 female recipients of male kidneys showed the lowest graft survival: donor/recipient male/female 89%; donor/recipient female/male 97%; no mismatch 97% (P=.01). CONCLUSIONS: Female recipients of male kidneys may experience a greater risk of early graft loss compared with all other gender combinations.

Association of rs10918594 polymorphisms of nitric oxide synthase 1 adaptor protein (NOS1AP) with QTc interval prolongation during kidney transplantation.

BACKGROUND: The mechanisms of sudden cardiac death are difficult to recognize, but repolarization disturbances have been shown to be the cause. The purpose of this study was to investigate whether the polymorphism of nitric oxide synthase 1 adaptor protein (NOS1AP) was related to the risk of occurrence of corrected QTc-interval prolongation and ventricular arrhythmias recorded on electrocardiography (ECG) Holter monitoring in kidney transplant recipients. STUDY DESIGN: The 75 adult first kidney transplant patients included 43 men with an overall mean age of 45±12 years (range, 20-68). Additional patient monitoring during the procedure and in the postoperative period consisted of a continuous ECG tracing recording and investigation of the rs10918594 NOS1AP polymorphism. RESULTS: We observed Transient QTc-interval prolongation during the perioperative period. NOS1AP genotypes were in Hardy-Weinberg equilibrium. For further statistical analysis, we combined GG homozygotes and CG heterozygotes because of the small numbers available; therefore, only a dominant mode of inheritance was investigated. There were no gender differences in QTc-interval patterns. Analysis of variance with repeated measures revealed no interaction between NOS1AP and QTc-interval values taken at various times among the kidney recipients. CONCLUSIONS: The transplantation procedure may lead to dynamic repolarization disturbances, which may produce an increased risk of severe arrhythmias despite optimization of patient status. The NOS1AP rs203462 polymorphisms did not correlate with an increased risk of QT interval prolongation among kidney recipients.

Graft infection in kidney recipients and its relation to transplanted kidney function.

INTRODUCTION: Following kidney transplantation, septic complications are the leading causes of therapeutic failure including recipient death or graft removal. The serum creatinine level is one of the earliest metrics of kidney metabolic function. We examined the influence of graft infection on serum creatinine levels in kidney recipients. STUDY DESIGN: We analyzed the function of 220 kidneys transplanted in nine centers in Poland. The kidneys were recovered from 146 multiorgan donors. Donor urea and creatinine levels were within the normal range. We investigated the influence of perioperative graft infection incidence on recipient creatinine levels at 1, 2, 3, 7, 14, 30, 90, and 180 days after kidney transplantation. The association of the serum creatinine level with categorical variables was assessed using either Student t test analysis of variance and multivariate techniques. In all analyses P<.05 indicated statistical significance. RESULTS: There were 25 graft infections revealing a significant relationship with increased recipient serum creatinine level after kidney transplantation (P=.003). Multivariate analysis confirmed the impact of infection. CONCLUSION: Perioperative kidney graft infection influenced graft funtion in the early and late periods post-transplantation.

The outcomes of treatment and the etiology of lymphoceles with a focus on hemostasis in kidney recipients: a preliminary report.

BACKGROUND: The etiopathogenesis of lymphoceles remains incompletely understood. The aim of our work was to analyze the perturbations of blood coagulation process for their possible impact on the etiology of lymphoceles. Additionally we performed an evaluation of the incidence and effectiveness of treatment methods for lymphoceles. MATERIALS AND METHODS: During 2004 to 2010, we performed 242 kidney transplantations in 92 female and 150 male patients. The hemostatic parameters included concentrations of: antithrombin, plasminogen, thrombin/antithrombin complexes (TAT), prothrombin products F1+2 (F1+2), d-dimers, and plasmin/antiplasmin complexes. RESULTS: At 7 years follow-up 27 (11%) recipients had developed symptomatic lymphoceles, namely abdominal discomfort, a palpable mess in the lower abdomen, arterial hypertension, infection of the operative site with fever, lymphorrhoea with surgical wound dehiscence, decreased diurnal urine output with an elevated plasma creatinine, voiding problems of urgency and vesical tenesmus, and/or symptoms of deep vein thrombosis. We applied the following methods of treatment aspiration alone, percutaneous drainage, laparoscopic fenestration or open surgery. In two only patients did perform open surgery. Since 2008 we have not performed an aspiration alone because of high rate of recurrence (almost 100%) and abandoned open surgery in favor of a laparoscopic approach. Our minimally invasive surgery includes percutaneous drainage guided by ultrasound and a laparoscopic procedure with 100% effectiveness. The examined hemostatic parameters revealed decreased concentrations of TAT complexes and F1+2 in subjects with lymphocele showing positive predictive values of 33% and 41% respectively. The negative predictive values for TAT complexes and F1+2 were 14% and 10%, respectively, suggesting decreased blood coagulation activity among effected recipients. Altered blood coagulation processes may explain some aspects of the disturbances of postoperative obliteration of damaged lymphatic vessels and formation of pathological lymph collection afterward. CONCLUSIONS: Perturbations of blood coagulation may be one cause for a lymphocele.

Histopathologic evaluation of pretransplantation biopsy as a factor influencing graft function after kidney transplantation in 3-year observation.

BACKGROUND: Many factors affect long-term results in kidney transplantation including histologic damage as a independent predictor, eg, chronic allograft dysfunction (CAD) in protocol biopsies and age-dependent lesions. Histopathologic findings correlate with the incidence of delayed graft function, eventual renal function, and allograft survival, allowing a rather precise prediction of graft outcomes. PATIENTS AND METHODS: We analyzed 92 thick-needle preimplantation renal biopsies and 29 from grafts after explantation. They had been preserved in 4% formalin and immersed in paraffin. Evaluable specimens contained ≥10 glomeruli and ≥2 arterial cross-sections. We analyzed tubulitis, intensity of acute tubular necrosis (ATN), inflammatory infiltration, glomerulonephritis, arterial hyalinization, arteritis, fibrosis, tubular atrophy, arterial intimal fibrosis, increased mesangial matrix, and glomerulosclerosis percentage, although for comparative analysis not only optimal ones were taken into consideration. Over postoperative time, we analyzed patient condition, urine output, serum concentrations of creatinine, urea, uric acid, and ions as well as necessity for postoperative dialysis, ie, delayed graft function (DGF). During the 3-year observation we analyzed living recipients, graft loss, death with a functioning graft, incidence of dysfunction (CAD), and acute rejection episodes (ARE). RESULTS: We observed significant correlations between immediate graft function (IGF) and lack of ATN in the pretransplantation biopsy. The presence of ATN significantly correlated with DGF and primary graft non-function. There was no correlation between renal function and arterial hyalinization or fibrosis, inflammatory infiltration, and tubular atrophy. Over postoperative time we observed significant correlations between IGF and the lack of interstitial fibrosis as well as significantly lower levels of creatinine, urea, and potassium as well as greater urine output early after transplantation. IGF correlated with shorter time to reach a creatinine level of 2 mg/dL, lower concentrations of creatinine, urea, and potassium, as well as greater diuresis during the first 5 days. In addition, lower creatinine and urea concentrations after 1 month and of urea at 6 and 36 months were associated with IGF. Female recipients showed lower concentration of creatinine over 3 months, of urea during the 1st day, and of potassium at 1 month; however, thereafter the differences were not significant. Better function of the right kidney was observed. The presence of severe ATN (ATN III) correlated with lower creatinine concentrations at 6 months and urea after 3 years. The presence of hyalinization in biopsies correlated with higher concentrations of urea at 1 year and of borderline significance after 3 years; surprisingly, potassium concentrations were lower after 2 and 3 years. The presence of inflammatory infiltrates correlated with higher creatinine concentrations after 1 and 3 years; similar correlations, albeit of borderline significance, were observed in tubular atrophy. Interstitial fibrosis correlated with creatinine concentrations during 10 days after the operation and after 12 months, also with potassium concentrations 5 days after the operation. Borderline correlations were observed between donor age and creatinine concentration in the first day after the operation, after 6 months, and time to achieve a creatinine concentration of 2 mg/dL. We observed that biopsies with greater numbers of glomeruli correlated with better graft function, namely, lower creatinine concentrations after 5 days as well as at 1 and 6 months, as well as lower urea concentrations after 5 days and 6 months. We also observed differences in renal function depending on gender. The presence of acute tubular necrosis, arterial fibrosis and a lack of inflammatory infiltration in pretransplantation biopsy correlated with worse late renal function. Explantation biopsies showed signs of CAD in 66.4% and histologic features of ARE in 38.51%.

An age-related decrease in factor V Leiden frequency among Polish subjects.

Factor V Leiden (G1691A FV mutation) is a widely acknowledged risk factor of deep vein thrombosis, including pulmonary embolism as the most serious complication. However, its high prevalence of ~5%in the Caucasian population might be related to an unknown evolutionary advantage. It might exert a beneficial effect on the carrier, e.g. protecting women from excessive bleeding during labour or allowing increased survival in severe sepsis or with other inflammatory diseases. The aim of our study was to verify or contradict the hypothesis of a favourable association between the A allele (A1691) and longevity in the Polish population. For this purpose, the G1691A mutation was analyzed by PCR-RFLP in 1016 Poles: 400 neonates (187 female and 312 male), 184 healthy adults (129 female and 55 male), and 432 long-lived individuals (age ≥95 years: 343 women and 89 men). Frequencies of G1691A carriers and the A1691 allele in long-lived individuals (0.2% and 0.1%, respectively) were significantly lower than in neonates (4.2% and 2.2%, respectively) and adults (3.3% and 1.6%). The frequency of the G1691A factor V Leiden mutation decreased with age, which indicates a shorter survival time among A1691 allele carriers in the Polish population.

Lack of association of polymorphisms 239+34A/C in the SOD1 gene and 47C/T in the SOD2 gene with delayed graft function and acute and chronic rejection of kidney allografts.

The superoxide dismutases (SODs) seem to be the most important enzymes involved in defense against reactive oxygen species, in particular against superoxide anion radicals. We hypothesized that genetic variability of antioxidant enzymes may have a role in development of these complications. The objective of the present study was to examine the association between polymorphisms 239+34A/C in the SOD1 gene or 47C/T in the SOD2 gene and development of delayed graft function (DGF) and acute or chronic rejection. The study included 187 recipients of first renal transplants. Patient history was analyzed taking into account DGF, acute rejection episodes, and chronic rejection. The polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. There were no significant associations between the polymorphisms and DGF or acute or chronic rejection. Our findings suggest that polymorphisms in SOD1 and SOD2 are not associated with development of either DGF or acute or chronic rejection.

Association of the A1936G (rs203462) of A-kinase anchoring protein 10 polymorphisms with QT interval prolongation during kidney transplantation.

INTRODUCTION: The purpose of this study was to investigate whether the polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) was related to the risk of occurrence of potentially dangerous arrhythmias during kidney transplant. METHODS: We performed this prospective observational study with additional patient monitoring during the kidney transplant procedure and in the postoperative period with continuous electrocardiogram (ECG) - (digital holter; ECG monitor type 300-7 Suprima system; Oxford, UK). After manual trace analysis, we performed classification of arrhythmias by interval measurement (including QT correction according to Bazett's formula: Qtc = QT/RR1/2), ST segment analysis within all channels, and analysis of heart rate variability (HRV) parameters (time analysis: SDNN as total rate variability measure, SDANN as long-term variability measure, SDNNindex, rMSSD and pNN50 as short-term variability measure) as well as frequency measure of power width parameters in the spectrum between 0.0033 Hz and 0.4 Hz. Subsequently applying polymerase chain reaction restriction fragment length polymorphism methods, we investigated A1936G (rs203462) AKAP10 polymorphism among 54 kidney recipients. RESULTS: Analysis of variance showed that prolongation of the QTc interval associated with the variant genotypes (GG + AG) was significantly greater compared with the AA genotype among kidney recipients (P = .04). We did not observe a relationship between the AKAP10 polymorphism and other arrhythmias, or clinical or environmental factors. CONCLUSIONS: Our data suggested that the AKAP10 (rs203462) GG + AG variation was associated with an increased risk of severe arrhythmias during kidney transplantation.

Plasma concentrations of TNF-alpha and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease.

Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrations of TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-alpha, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors.

Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection.

Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering on chromosome 3p21. Here the influence of 5 genetic variants was studied: Delta32 CCR5, G(-2459)A CCR5, G190A CCR2, G744A CX3CR1 and C838T CX3CR1. They were screened in a cohort of 168 HIV-1 positive adults [HIV(+) group] and 151 newborns [control group] from northwestern Poland. PCR-RFLP was performed to screen for the variants (except for Delta32 CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for the CCR5 polymorphisms, with the Delta32 allele and the (-2459)A CCR5 allele more frequent among neonates than in the HIV(+) group. No Delta32/Delta32 homozygotes were found in the HIV(+) group, but 16.1 percent were Delta32/wt heterozygotes. In the control group, 1.3 percent; were Delta32/Delta32 homozygotes and 26.0percent were Delta32/wt heterozygotes. Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes containing Delta32 CCR5, 190G CCR2 and 744A CX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and resistance to HIV-1 infection.