Wanda Trautsolt

G-Protein β3 Subunit C825T Variant, Nephropathy and Hypertension in Patients with Type 2 (Non-Insulin-Dependent) Diabetes mellitus

Background: There is substantial evidence that hereditary factors contribute to the predisposition to diabetic nephropathy. On the other hand, it has been suggested that genetics of diabetic nephropathy and hypertension may overlap. Recently, a C to T substitution (C825T) in the gene encoding for the guanine-nucleotide-binding protein β3 subunit (GNB3) was identified, and this molecular variant was found to be associated with enhanced activation of G proteins and increased risk of the development of hypertension. The aim of the study was to test whether GNB3 C825T polymorphism contributes to the development of incipient or overt nephropathy or hypertension in type 2 diabetic patients. Methods: GNB3 genotype was determined in 130 type 2 diabetic patients with overt proteinuria or chronic renal failure, 155 diabetic patients with microalbuminuria and 163 control subjects with normoalbuminuria and known type 2 diabetes duration of at least 10 years. Results: No differences in GNB3 genotype distributions or allele frequencies between the study groups were found. Also, no differences between normotensive and hypertensive patients were demonstrated. Conclusion: The study provided evidence against the major impact of the GNB3 C825T polymorphism on the increased risk of the development of nephropathy or hypertension in type 2 diabetic patients.

PTPN22 Polymorphism Presumably Plays a Role in the Genetic Background of Chronic Spontaneous Autoreactive Urticaria

Background: The association of chronic urticaria (CU) with autoimmune disorders is relatively well proved. Protein tyrosine phosphatase-22 (PTPN22) is considered to be one of the strongest genetic factors for human autoimmunity. We decided to evaluate whether additional, non 1858C>T, PTPN22 variants are independent contributors to the risk of CU occurrence in the Polish population. Methods: A total of 91 CU patients with a positive result of autologous serum skin test and 100 healthy volunteers were enrolled in the study. The Urticaria Activity Score was used in disease intensity assessment. In all subjects rs3811021, rs1310182 and rs2488457 polymorphisms were genotyped. Results: We found a higher prevalence of –1123 C allele among CU patients. No differences in the allele and genotype distribution were found in the other analyzed polymorphisms. Haplotype construction of the three SNPs revealed statistically significant CU association of rs2488457C, rs1310182T and rs3811021T. Conclusions: Contrary to previous findings, the contribution of PTPN22 to disease susceptibility is suggested. We can speculate that CU is a genetically complex disease and that its occurrence needs multiple genetic and environmental risk factors.

Protein tyrosine phosphatase‐22 (PTPN‐22) polymorphism in the pathogenesis of chronic urticaria

patients described difficulty in breathing following ingestion of cooked and uncooked nuts (four with peanuts and three with various tree nuts). One patient reported similar symptoms after eating raw carrots. A variety of plant-derived foods were reported to reproducibly cause diarrhoea soon after exposure in 4 of 24 patients, including apple, pear, banana, melon, tomato. Finally, facial angioedema was reported within 30 min of eating raw peach in one patient and raw apple in another. Aside from positive results for PR-10 proteins, none of these patients were sensitised to nsLTP or type 1 allergens. These symptoms were selflimiting in all cases and were not a universal indication for prescription of epinephrine autoinjector devices. To summarise, PFS was closely associated with sensitisation to the PR-10 protein cluster in this small UK cohort. Not all patients have spring rhinitis, highlighting the importance of investigation for panallergen sensitisation regardless of rhinitis history in patients with appropriate symptoms. Profilin sensitisation was a clinically relevant co-factor in some patients, but sensitisation to nsLTP was of uncertain clinical significance. Recent publications have highlighted a possible role for nsLTP outside of the Mediterranean in the context of peach allergy (4) and hazelnut allergy (5) and larger studies of UK patients will be required to explore this further.

Polymorphic Genes for Kinin Receptors, Nephropathy and Blood Pressure in Type 2 Diabetic Patients

Background/Aims: There is evidence that hereditary predisposition contributes to the development of diabetic nephropathy and hypertension. Polymorphisms in the genes for bradykinin receptors (B1R and B2R) were found to be associated with decreased risk of the development of end-stage renal disease. This study examines whether B1R G–699C and B2R C181T polymorphisms are associated with microalbuminuria or overt nephropathy, or blood pressure variation in type 2 diabetic subjects. Methods: B1R and B2R polymorphisms were determined in 153 type 2 diabetic patients with microalbuminuria, 132 with overt nephropathy (macroalbuminuria or chronic renal failure), and 161 patients with normoalbuminuria despite diabetes duration longer than 10 years. Results: Distributions of the examined polymorphisms did not differ between patients with microalbuminuria or overt nephropathy, compared to normoalbuminuric control subjects. Patients carrying the B2R T allele had lower DBP, compared with non-carriers: 83.6 ± 12.0 vs. 87.4 ± 12.1 mm Hg, p < 0.05. Among patients not receiving ACEI, both SBP and DBP was significantly lower in B2R T allele carriers, compared to non-carriers (137.2 ± 20.3 vs. 146.5 ± 21.7 mm Hg, and 80.3 ± 11.9 vs. 85.8 ± 11.6 mm Hg, p < 0.05). Conclusions: Examined polymorphisms are not associated with the increased risk of incipient or overt nephropathy in type 2 diabetic patients. B2R C181T polymorphism may contribute to blood pressure variation in these subjects.

CTLA-4 polymorphism in the pathogenesis of chronic spontaneous autoreactive urticaria

BACKGROUND Autoimmune mechanisms are considered to play a significant role in chronic urticaria pathophysiology. Additionally, clinical experience emphasises the coexistence of chronic urticaria manifestation with thyroid autoimmunity. As the role of CTLA-4 polymorphism in autoimmune thyroid diseases is well proven we speculated on the possible role of this polymorphism in the background of chronic urticaria. MATERIALS AND METHODS We included 128 chronic spontaneous autoreactive urticaria patients (87 females and 41 males) and 101 healthy volunteers (71 females and 30 males). In all examined subjects CTLA-4 A49G polymorphism was analysed. Disease severity with Urticaria Activity Score as well as age of disease onset was also studied. RESULTS No statistically significant differences in the allele or genotype distribution between urticaria patients and controls were observed. Furthermore, we found no association between CTLA4 polymorphism and urticaria severity as well as the age of disease onset. CONCLUSIONS Our data suggest that there is no contribution of CTLA-4 A49G polymorphism to chronic spontaneous autoreactive urticaria susceptibility. We recommend further research on other polymorphisms in chronic urticaria patients to explore in detail the potent role of the genetic background in the pathogenesis of this disorder.

Possible contribution of chemokine receptor CCR2 and CCR5 polymorphisms in the pathogenesis of chronic spontaneous autoreactive urticaria.

BACKGROUND Autoimmune mechanisms play a role in the pathophysiology of chronic urticaria. As the genetic background of autoimmunity is well proven, the role of genetics in chronic urticaria is hypothesised. METHODS 153 unrelated chronic spontaneous urticaria patients with a positive result of autologous serum skin test were included into the study, as were 115 healthy volunteers as control group. In all subjects we analysed CCR2 G190A and CCR5 d32 polymorphisms. RESULTS We noticed higher prevalence of CCR2 A allele as well as lower frequency of CCR5 d32 in chronic urticaria group in comparison to control group, with borderline statistical significance. Additionally, we assumed haplotype Gd statistically significant negative chronic urticaria association with tendency to higher frequency of Aw haplotype in this group. CONCLUSIONS The results of our study imply the role of autoimmune components in chronic urticaria pathogenesis and present chronic urticaria as possibly genetically related disorder.

Association of rs 3807337 polymorphism of CALD1 gene with diabetic nephropathy occurrence in type 1 diabetes — preliminary results of a family-based study

INTRODUCTION The worldwide growing burden of diabetes and end-stage renal disease due to diabetic nephropathy has become the reason for research looking for a single marker of chronic kidney disease development and progression that can be found in the early stages of the disease, when preventive action delaying the destructive process could be performed. The aim of the study was to investigate the influence of rs3807337 polymorphism of the caldesmon 1 (CALD1) gene located on the long arm of chromosome 7 encoding for protein that is connected with physiological kidney function on development of diabetic nephropathy. MATERIAL AND METHODS There was an association study of rs3807337 polymorphism of the CALD1 gene in parent-offspring trios by PCRRFLP method. Ninety-nine subjects: 33 patients with diabetic nephropathy due to type 1 diabetes and 66 of their biological parents, were examined. The mode of alleles transmission from heterozygous parents to affected offspring was determined using the transmission disequilibrium test. RESULTS The allele G of rs3807337 polymorphism of the CALD1 gene was transmitted to affected offspring significantly more often than expected for no association. CONCLUSIONS The obtained results suggest that the genetic variability of the CALD1 gene may influence the development of diabetic nephropathy in type 1 diabetes, but further studies involving larger studied groups of patients are needed. (Endokrynol Pol 2017; 68 (1): 13-17).

Inducible T-cell costimulator (ICOS ) and CD28 polymorphisms possibly play a role in the pathogenesis of chronic autoreactive urticaria

Clinical experience emphasizes the coexistence of chronic spontaneous urticaria (CSU) and autoimmune disturbances. In chromosome 2q33‐34, there is a cluster of homologous genes that are considered promising candidate genes for susceptibility to autoimmune diseases.

Interleukin 2 as a potential cancer marker in patients after kidney transplantation

INTRODUCTION Transplant recipients have a significantly greater incidence of cancer, compared with the general population, who are referred to immunosuppressive therapy as an additional malignancy risk factor. Therefore, there is a need to search for an easy in clinical practice neoplasm predictor, especially for this group of patients. MATERIALS AND METHODS A group of 74 (43M and 31F; aged 46.8 ± 12 years) kidney transplant recipients was investigated in a three-year follow-up study. During the time of observation, 7 patients were diagnosed with neoplasm (7.4 ± 1.5 years after transplantation). A serum level of IL2 (ELISA test) and mRNA level of IL1beta, IL10 and TNFalfa in peripheral mononuclear blood cells - PBMCs (QRT - PCR method) were measured in every year of observation. Analysis of variances and t-Student test were used in groups mean comparison: N - patients developing malignant neoplasm group (24 probes); M - set of probes from patients with malignancies at the moment of diagnosis (11 probes); P - set of probes from patients before developing malignant neoplasm (10 probes); C - control group of healthy transplant recipients (31 probes). RESULTS Among the analyzed agents, only serum IL2 level differed between the analyzed groups, with higher values in the M compared with the P group (p<0.05) and with C group (p<0.01). There were no differences neither between N and C or P and C groups (p = 0.98), nor any correlation between IL2 and IL1b, IL2 and TNFalfa. CONCLUSIONS The results may indicate that IL2 serum level might be consider as a useful late unspecific cancer marker, although larger studies should yield verification of this finding.

The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25-55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19-3.66) as well as the G allele (OR=1.49, 95% CI: 1.08-2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.