Izabela Klich

TGF-β1 gene polymorphisms and primary vesicoureteral reflux in childhood

The aim of this study was to assess the association between the transforming growth factor-β1 (TGF-β1) gene polymorphisms rs1800469 (commonly known as T-509C) and rs1982073 (commonly known as Leu 10→Pro) and primary vesicoureteral reflux (VUR) and renal scarring. Using a case–control approach, we examined 121 children with primary VUR and 169 controls. Genotyping of the TGF-β1 gene polymorphisms was performed by restriction fragment length polymorphism (RFLP) analysis. The 99mTc-DMSA– or 99mTc-unitiol–single photon emission computed tomography method was used to evaluate renal scars in 84 of 121 VUR children. Statistical analysis revealed differences in rs1800469 genotype frequencies between VUR patients and controls (p = 0.0021). Our data demonstrate that individuals homozygous for the TT genotype are at risk of primary VUR [odds ratio (95% confidence interval) = 2.7 (1.46–5.08)]. Distribution of the rs1982073 polymorphism was similar in VUR children and controls. In terms of renal scarring, patients were stratified into non-scar and scar subgroups, and no differences in the genotype frequencies of either polymorphism was found. Previous reports have shown that the TT genotype of the rs1800469 polymorphism is a risk factor for renal scarring in primary VUR, and the results of our study suggest that this same polymorphism is associated with susceptibility to this congenital uropathy.

APBB2 genetic polymorphisms are associated with severe cognitive impairment in centenarians

APBB2 gene encodes for β-amyloid precursor protein-binding family B member 2, (APBB2, FE65-like, FE65L1), an adaptor protein binding to the cytoplasmatic domain of β-amyloid precursor protein (βAPP). Over-expression of APBB2 promotes formation of β-amyloid (Aβ), the main constituent of senile plaques. Polymorphisms within APBB2 gene have been proposed as candidate risk factors for Alzheimers disease. However, their association with longevity has never been investigated. Here we present the first attempt to analyze APBB2 polymorphisms in centenarians. We used a PCR-RFLP method to analyze two intronic nucleotide substitutions: hCV1558625 (rs17443013) and rs13133980. We found no differences in genotype or allele distribution between centenarians and young controls. After stratification of centenarians upon their cognitive performance, the APBB2 rs13133980 G allele was over-represented in centenarians with severe cognitive impairment compared to individuals without this disability. Also the hCV1558625-rs13133980 AG haplotype increased relative risk for severe cognitive impairment in centenarians. Our results support the concept of APBB2 polymorphism association with cognitive performance in the oldest age.

ICOS Gene Polymorphism May Be Associated with Pemphigus

Background: Pemphigus is an autoimmune blistering disease mediated by circulating IgG autoantibodies directed against desmogleins 3 and/or 1. As pemphigus is a T cell–mediated disease, one may assume that genetically determined disregulation of costimulatory signal may be involved in its pathogenesis. Objective: The aim of the present study was to evaluate the relationship between polymorphisms in genes encoding costimulatory receptors, CTLA4 and ICOS, and pemphigus in the Polish population. Methods: The study included 54 patients with pemphigus: 40 with pemphigus vulgaris (PV) and 14 with pemphigus foliaceus (PF). Additionally, 176 healthy unrelated blood donors served as controls. +49A/G CTLA4 and IVS1+173 ICOS polymorphisms were identified using a modified polymerase chain reaction–restriction fragment-length polymorphism. Results: Analysis of the frequency of genotypes and alleles of +49A/G CTLA4 gene polymorphism showed no statistically significant differences between the PV and PF patients and the controls. The distribution of genotypes in IVS1+173 ICOS polymorphisms was significantly different in both PV (p < .01) and PF (p = .0004) patients when compared to controls. The carriers of the allele C were more frequent in PV or PF in comparison with the control group (p < .001 for both groups). Conclusions: Our results suggest that genetically determined abnormal function of costimulatory receptors in T cells may be associated with the pathogenesis of pemphigus.

The prion protein M129V polymorphism Longevity and cognitive impairment among Polish centenarians

The PRNP gene encodes the cellular isoform of prion protein (PrPc). The M129V polymorphism influences the risk of prion diseases and may modulate the rate of neurodegeneration with age. We present the first study of the polymorphism among Polish centenarians. In the control group (n = 165, ages 18 to 56 years) the observed M129V genotype frequencies agreed with those expected according to the Hardy-Weinberg equilibrium (MM, MV, VV): 43%, 44%, 13% (HWE p > 0.05). Among centenarians (n = 150, ages 100 to 107) both homozygotes were more common than expected and HWE was rejected: 46%, 37%, 17% (expected 42%, 46%, 13%; HWE p = 0.025). This finding is consistent with a higher mortality rate among heterozygotes. However, the observed allele and genotype frequencies did not differ significantly between the oldest-old and the young controls. The genotypic frequencies were not related to severe cognitive impairment among the centenarians.

Effect of vitamin D receptor gene (VDR) polymorphism on body height in children – own experience

UNLABELLED Genetic and environmental factors have an influence on the process of growth and development of the body. One of numerous genetic factors can be the vitamin D receptor gene (VDR). The study aimed at evaluating the relationship between VDR polymorphism and somatic parameters in children. PATIENTS AND METHODS The study group consisted of 395 children, aged 6-18 years. All the patients underwent gene typing using the PCR-RFLP method within polymorphic loci BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236) of the VDR receptor gene. 294 children made up the control group in the study on the incidence of particular genotypes; in 161 patients somatic measurements of body weight and height were made with standard methods and skeletal densitometry (total body and spine programmes) examination was performed. Statistica 10.0 PL was used for statistical analysis. RESULTS In patients with low bone mass a relationship between body height and FokI VDR polymorphism was noted. The p-value was statistically significantly different in group I (p=0.002) and borderline significant in group III (p=0.09). None of the polymorphisms of the VDR receptor gene demonstrated any statistically significant differences in anthropometric values in the control group and in children with osteoporosis. SUMMARY The presence of the F allele of FokI polymorphism of the VDR receptor gene results in increased height, which is best observed in children with low bone mass. The FF genotype favours increased height in the study group of children from Łódź.

Selected risk factors of fractures in children — own observation

Bone fractures may depend on Vitamin D Receptor Gene (VDR), bone mineral density, bone turnover markers. Patients and methods. 161 patients were recruited and underwent: skeletal densitometry (DXA) method and bone turnover studies (Osteocalcin and Ntx).The study group was evaluated using restriction enzyme digestion at BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236), polymorphic sites of the VDR gene. Multivariate logistic regression was used to assess factor significance. The model included variables with sex- and age-standardized parameters, VDR genotypes, and bone metabolism marker levels. Results. Factors associated with fractures were: osteocalcin concentration and Z-score BMDt. Odds Ratio (OR) values equaled: 1.01 (95%Confidence Interval (95%CI) 1.00–1.02) for osteocalcin (p=0.006), and 0.66 (95%CI 0.42-1.03; p=0.07) for Z-score BMDt. In patients with reduced bone mass, factors related to fractures were: osteocalcin (0.04) and carriage of BsmI b (0.07) or ApaI a alleles (0.08). ORs were 1.01 (95%CI 1.00–1.02) for OC, 0.29 (95%CI 0.07–1.14) for BsmI, and 2.13 (95%CI 0.91–4.99) for ApaI polymorphic allele carriage. Conclusions. Carriage of BsmI b allele reduces, while carriage of ApaI a allele and heightened osteoclacin level increase the risk of fractures in study children with reduced bone mass. VDR polymorphism, bone mineral density and bone formation’s marker — osteocalcin maybe considered as risk factor for fracure in children from Lodz region.