Cardiovascular diseases and G-protein beta3 subunit gene (GNB3) in the era of genomewide scans.
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Biomedical subjects
Publications and source records attributed to W Grzeszczak.
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BACKGROUND: The XbaI polymorphism in the glucose transporter GLUT1 gene has been implicated in the development of diabetic nephropathy in Chinese type 2 diabetes patients. METHODS: To examine whether the XbaI polymorphism is involved in the development of diabetic nephropathy in Caucasian type 2 diabetes patients, a large case control study was performed. The study group of 444 patients with type 2 diabetes consisted of three subgroups: 162 patients with normoalbuminuria (only patients with duration of type 2 diabetes of at least 10 years after diagnosis); 150 with microalbuminuria; and 132 subjects with persistent proteinuria or chronic renal failure (CRF). The polymerase chain reaction (PCR)-based genotyping of the XbaI polymorphism was performed in each subject. RESULTS: The genotype distribution in the subgroups showed an increased frequency of the (+/+) genotype in patients with microalbuminuria (41%; OR 1.40, 95% CI, 0.89 to 2.24) and proteinuria/CRF (47%; OR 1.82, 95% CI, 1.13 to 2.93, P = 0.013) when compared with normoalbuminuria (33%). No difference in the genotype distribution was observed between type 2 diabetes patients and healthy controls. CONCLUSIONS: The results of this study in Caucasian patients with type 2 diabetes indicate that the XbaI(-) allele in the GLUT1 gene protects against the development of diabetic nephropathy. Our results are in contrast to the case control study in Chinese patients with type 2 diabetes in which the presence of the XbaI(-) allele appeared to have a strong association with the development of diabetic nephropathy.
BACKGROUND: Because of the heterogeneous aetiology of kidney diseases, interactions between multiple genetic and environmental factors are thought to be involved in the process of progression to end-stage renal disease (ESRD). Raised blood pressure remains a well-established, independent risk factor for a more rapid decline of renal function in various kidney diseases. The aim of the study was to investigate the role of the human SA gene Pst1 polymorphism in the development and/or progression of chronic renal failure (CRF). METHODS: This polymorphism was genotyped in a group of 247 family trios (offspring affected with end-stage renal disease, and both parents): 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with diabetic nephropathy. Transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring. RESULTS: SA gene Pst1 allele transmission did not differ from random proportion of 50:50, with no significant variation in the slope of reciprocal serum creatinine over time between patients with SA Pst1 A1A1, A1A2, and A2A2 genotypes. In addition, no impact of this marker on the rate of progression of CRF in the course of diabetes mellitus, interstitial nephritis, and chronic glomerular nephritis was shown. CONCLUSION: Results of the study suggest no major role of SA gene polymorphism in promoting renal damage. However, the limited numbers of patients having both parents alive included in the analysis might have resulted in insufficient power to detect a minor impact of this polymorphism, especially if such effect is confined to a certain aetiology of CRF.
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OBJECTIVE: In patients with clinical hemochromatosis, the frequency of diabetes ranges from 20 to 50%, and the heterozygosity for the C282Y mutation in the HFE gene might be associated with an increased risk for diabetes. There are also some reports that suggest that iron overload might cause diabetic nephropathy. RESEARCH DESIGN AND METHODS: We performed an association study to assess the role of the C282Y and H63D mutations in the HFE gene as a risk factor for type 2 diabetes and diabetic nephropathy. Altogether, 563 patients with type 2 diabetes were included in the study. In the analyzed group, 108 patients had overt proteinuria, 154 had microalbuminuria, and 301 had normoalbuminuria. Among the patients with normoalbuminuria, only those with known diabetes duration > or = 10 years were considered normoalbuminuric (n = 162). A total of 196 unrelated healthy subjects were used as a control group. All subjects were genotyped for C282Y and H63D using the polymerase chain reaction-based protocol. RESULTS: There was an increased frequency of 282Y allele carriers among patients with type 2 diabetes versus healthy control subjects (OR 5.3, 95% CI 1.6-17.3). We observed an increased frequency of the 63D allele carriers among patients with diabetic nephropathy (1.8, 1.2-2.8). CONCLUSIONS: In conclusion, our study is the first to indicate that being a carrier of the H63D hemochromatosis mutation is a risk factor for nephropathy in type 2 diabetic patients. We also confirmed previous observations that the frequency of the 282Y mutation was higher in patients with type 2 diabetes than it was in the general population of healthy subjects.
The pathogenesis of hypertension in diabetes type 1 and type 2 is different. Diabetic nephropathy is regarded as the most essential factor contributing to the development of hypertension in patients with diabetes mellitus type 1. Obesity, insulin resistance and hyperinsulinaemia are responsible for hypertension in diabetes mellitus type 2. In both types of diabetes, hypertension is involved in fast progress of diabetic renal disease. Antihypertensive treatment in diabetic patients should include: non-pharmacological interventions, drug-therapy, regular blood pressure monitoring, educational efforts. ACE-inhibitors, calcium antagonists, diuretics, beta-blockers, angiotensin II receptor antagonists and alpha 1-blockers are used as antihypertensive agents in diabetic patients. Neutral endopeptidase inhibitors are the new, promising therapeutic option.
The aim of the study was to evaluate whether in diabetics with good metabolic control and without any diabetic complications, disturbances of calcium, phosphorus and magnesium metabolism or hormonal regulation (parathormone/calcitonin) were present, and if they depended on type of diabetes, duration time of diabetes, kind of hypoglycaemic treatment, sex or age of patients. 83 subjects were examined, including: 14 with type 1 diabetes mellitus, 49 with type 2 diabetes mellitus and 20 healthy persons. All tests were performed in standarized low-calcium diet conditions. In basal conditions both serum concentrations and daily urine excretion of calcium, phosphorus, magnesium were estimated. Oral and intravenous calcium load tests with simultaneous parathormone, calcitonin, calcium, magnesium and phosphorus concentrations estimation were done. The final conclusions were as follow: Both in type 1 diabetes mellitus and type 2 diabetes mellitus subjects with good metabolic compensation and without advanced diabetic complications a tendency to early disturbances of calcium-phosphorus metabolism is observed. Physiological hormonal control (parathormone/calcitonin) is preserved. Correlations between mineral metabolism and type of diabetes, duration time of diabetes, daily insulin dose, body mass index and sex are observed. Kind of hypoglycaemic treatment has only slight influence on the mineral metabolism.
Both high morbidity and potentiation of systemic complications emphasise significance of diabetes mellitus and hypertension co-incidence. The aim of the study was to analyse the influence of hypertension accompanied with type 2 diabetes mellitus on calcium phosphorus and magnesium metabolism. The study was performed in standard low-calcium diet conditions on the group of 49 patients with type 2 diabetes mellitus (among them 27 had hypertension), 14 patients with essential hypertension and 20 healthy persons. Both serum and urine concentration of creatinine, calcium, phosphorus, hydroxyproline, hydroxylysine and uric acid were analysed. Oral calcium load test was done. Serum alkaline phosphatase activity and oxalic acid urine excretion were also estimated. There were no significant differences between diabetic patients with and without hypertension as far as calcium, phosphorus or magnesium metabolism were concerned.
The resorption and osteogenesis equilibrium is commonly known basal condition of bone tissue homeostasis. For the purpose of bone turnover analysis in the group of good controlled diabetic patients without any diabetic complications basal biochemical parameters of osteogenesis and resorption were estimated. During low-calcium diet conditions both serum concentration and urine excretion of creatinine, hydroxyproline, hydroxylysine and uric acid were investigated. Serum alkaline phosphatase activity and oxalic acid urine excretion were also measured. As the result of the study the higher serum alkaline phosphatase activity and hydroksyproline urine excretion in type 1 diabetic patients as well as higher hydroxyproline and hydroxylysine urine excretion in type 2 diabetic patients were found.
INTRODUCTION: There is strong evidence that the R576 allele of interleukin-4 receptor alpha gene (IL-4R) might predispose to atopy. To test this hypothesis, we examined the association between the R576Q polymorphism and atopy in a Polish population using the family-based study design. MATERIALS AND METHODS: 44 atopic patients (age range from 11 to 34 years) with pollen and house dust mite allergy or/and mild asthma together with both parents were studied. The R576Q polymorphism of the IL-4R gene was genotyped in each patient and both parents, respectively, using the PCR-based protocol. The results were analyzed by the transmission disequilibrium test (TDT). The total IgE serum level, allergen-specific IgE to the common aeroallergens, IL-4, and sIL-4Ralpha were assessed in each patient and both parents. RESULTS: In the TDT test the R576 and Q576 alleles were transmitted from the heterozygous parents to the affected offspring 20 and 15 times, respectively (McNemar test: p = 0.19). The results of the transmission disequilibrium test did not reach statistical significance. Thus, the R576 allele might contribute to the pathogenesis of allergic diseases in patients with high total IgE serum level (p < 0.05). A larger study group has to be studied to prove the observed linkage and association.
Patients with diabetes (type 1 or type 2) live shorter because of the long-term complications of hyperglycemia. One of the most important aims of therapy in diabetic subjects is delay in the development of long-term diabetes complications. However, another important aim of therapy in diabetic patients is the use of drugs, which not only delay the time of long-term complications development but also improve the quality of life. The paper presents the results of studies on quality of life in diabetic subjects basing on contemporary literature. In patients with type 1 diabetes mellitus a quality of life decreases gradually with the duration of diabetes. The influence of intensive insulin therapy on quality of life is minimal or absent. In UKPDS study no differences in quality of live between conventionally or intensively treated patients were observed. In subjects with macrovascular complications the quality of life is significantly worse. Generally, the authors of UKPDS suggested that better glycemic control is not associated with better quality of life. Only Testa and Simonsen demonstrated that type 2 diabetic subjects treated by new "intelligent" drug--glipizide GITS (Glibenese GITS) is associated not only with better metabolic control but also with better quality of life.
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BACKGROUND: Chronic renal failure (CRF) is a complex phenotype that results from an underlying kidney disease and superimposing environmental and genetic factors. The aim of our study was to evaluate the role of polymorphisms in the genes encoding for components of the renin-angiotensin system (RAS) in the development and/or progression of CRF. METHODS: Two hundred forty-seven family trios (patients with CRF and both parents; 120 with primary chronic glomerulonephritis, 80 with interstitial nephritis, and 47 with type 1 diabetes with nephropathy) were examined, and transmission/disequilibrium test (TDT) was used to evaluate allele transmission from heterozygous parents to affected offspring. RESULTS: The D allele of the angiotensin I-converting enzyme (ACE) gene insertion/deletion polymorphism was transmitted significantly more frequently than expected for no association among all examined trios and in the subgroup of patients with interstitial nephritis. The angiotensinogen 235T allele was transmitted significantly more frequently to patients with CRF than expected for no association, but the effect was seen only in patients with interstitial nephritis. The presence of the DD or ID genotype was associated with a faster rate of decline of renal function, which was not observed for the angiotensinogen M235T polymorphism. For chymase gene and angiotensin II receptor type 1 gene, allele transmission did not deviate significantly from a random proportion of 50:50%. CONCLUSIONS: The results of this study suggest that ACE gene insertion/deletion and angiotensinogen M235T polymorphisms contribute to the increased risk for the development of CRF, but the magnitude of the effect within subsets of patients with specific etiologies of CRF must be evaluated further.
BACKGROUND: Several studies have suggested that the same genetic factors may be involved in the predisposition to both essential hypertension and diabetic nephropathy, but the molecular mechanism underlying this predisposition still remains unclear. In particular, the role of genes involved in blood-pressure regulation and angiotensin II action is still controversial. This study examines a possible association between angiotensinogen M235T and chymase gene CMA/B polymorphisms with the presence of nephropathy in type II diabetic Caucasians. METHODS: For the purposes of the study, 323 microalbuminuric and 127 overt proteinuric cases, together with 243 normoalbuminuric controls with long-duration diabetes were selected from a group of 941 type II diabetic patients with established renal status. RESULTS: No differences in the genotype distributions or allele frequencies of the examined polymorphisms between the study groups were observed. The study groups were also stratified by gender, diabetes duration, level of glycaemic control, body mass index, hypertension, and retinopathy status, but still no distortion in the distributions of genotypes of any of the examined polymorphisms in any of the strata was shown. CONCLUSIONS: Our study provided evidence against an association between angiotensinogen M235T or chymase gene CMA/B polymorphisms and the presence of incipient or overt nephropathy in Caucasian patients with type II diabetes.
Doctors' and medical students' attitude to the primary prevention of hypertension is important, as this community is responsible for medical education. The level of acceptance for some antihypertensive strategies was assessed in 180 doctors and 300 medical students (263 women and 217 men). The study consisted of reading and filling the anonymous questionnaires. The necessity of primary prevention of hypertension in absolutely essential in medical education.
The aim of the study was to assess the prevalence of headaches and analgesic use in hypertensive patients and to evaluate the relationship between taking analgesic drugs and adherence to antihypertensive therapy. 754 consecutive hypertensive patients (446 women and 308 men, aged 18-89 years, median age--58 years) from 7 out-patient centres participated in the study. Anonymous questionnaires consisted of 13 simple questions concerning demographic parameters (age, gender), clinical data (the duration of hypertension and antihypertensive therapy), the history of headache and use of analgesics were distributed among the participants. Among the hypertensives participating in the study, 82.9% (625) reported headaches. Analgesics were used by 65.3% (408) of hypertensive patients with headaches. There was significant, positive linear correlation between the history of headaches and the duration of analgesic use in hypertensive patients. The rate of non-compliance was significantly higher among patients with headaches who reported regular use of analgesics when compared to non-users of analgesics. There were statistically more non-compliants among patients taking more than 1 type of analgesics than in hypertensives reporting use of only 1 analgesic drug. The prevalence of headaches and the rate of analgesic use is considerably significant among hypertensive patients. Analgesic consumption seems to be a risk factor for non-adherence to antihypertensive medication.