Biomedical subjects

Kamila Czerska

Publications and source records attributed to Kamila Czerska.

5 recordsLinked to original sources

PubMed2006

Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis.

OBJECTIVES: Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or predisposing to pancreatitis. The aim of this study was to evaluate the impact of these defects into molecular pathology of chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). METHODS: Ninety-two children with CP or ARP, 55 family members and 50 controls were investigated. The subjects were screened for PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1 N34S variant; panel of 14 CFTR defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8-T variant or panel of 3 CFTR defects-F508del, CFTRdele2,3 and IVS8-T; AAT mutations: E264V, E342K. RESULTS: We identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12 of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent. PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587). Overall frequency of AAT mutations was lower than in the controls. Family studies showed that defects in the examined genes did not always segregate with disease. CONCLUSIONS: PRSS1 defects seem to be causative for pancreatitis, whereas defects in SPINK1 are suggested to be associated with the disease. No association between CFTR mutations and pancreatitis was observed. The importance of AAT variants remains speculative.

Acute Disease↗

PubMedDate not supplied

[I. Single nucleotide polymorphism in human genetic analyses].

The new era of human genetic analyses has been began by finishing of The Human Genome Project. Discovery of the almost complete sequence of human DNA showed surprisingly small differences between the genetic materials of randomly chosen people. Genetists pay intensive attention to the very small part of nucleotide sequence - 0.1% - which contains polymorphic changes. The most frequent type of these changes is polymorphism of a single nucleotide (SNP). It makes up about 90% of all molecular differences in human DNA sequence. There are about 3 mln positions in DNA sequence containing SNPs. Polymorphic changes serve as genetic markers and they enable to map genes or to follow their inheritance. Changes of this kind seem also to be the possible cause of the remarkable variety of susceptibility to many common diseases e.g.: diabetes, cancer and cardiovascular disorders. SNPs are also the object of interest of intensively developing scientific domain - pharmacogenetics. Scientists working on this interdisciplinary field - connecting pharmacology and genetics - try to find out the reason of great variety of response to medicines and their side effects in case of patients belonging to the same therapeutical groups. Progress in this kind of research in near future will enable a significant improvement of pharmacological therapy, which will be based on matching the drug to genetically determined traits of patients.

Genetic Markers↗

PubMedDate not supplied

[Prenatal diagnosis of cystic fibrosis in risk families in Poland--results of molecular analysis].

BACKGROUND: Cystic fibrosis is one of the most common genetic disorders in the Caucasian population, inherited as an autosomal recessive trait. Diagnosis of CF classifies the patient's family to the group of high genetic risk. In spite of the significant therapeutic advantages this disease is still the cause of preterm death of affected patients. One of the diagnostic tests that are offered to CF risk families is prenatal diagnostics of the disease. This kind of analysis may be performed in the first trimester of pregnancy and is based on the DNA analysis of the foetus. AIM: To sum up and analyse the results of CF prenatal diagnostic studies, in Poland, in the period 1990-2003. MATERIAL AND METHOD: In total 45 tests in 38 risk families have been carried out. In case of 7 families in formative results have been obtained due to application of the polymorphic markers analysis. In the remaining cases molecular analysis of foetal DNA focused on identification of specific CFTR gene mutations has been carried out. RESULTS: In 16 cases the CF genotype was identified. The disease was excluded in 29 foetuses. Some issues of genetic counselling in the context of the possibility of prenatal disease diagnosis have also been discussed.

Cystic Fibrosis↗

PubMedDate not supplied

[Cystic fibrosis--a disease with many faces. The variable clinical picture versus the heterogeneity of molecular defect].

Cystic fibrosis (CF) is the most common genetic disorder in the Caucasian population with an autosomal recessive mode of inheritance. The disease is caused by mutations in the CFTR gene. So far, over 1300 of them have been identified. Primarily, the disease affects the epithelial cells of the airways, pancreas, intestines, gall bladder and sweat glands. However, cystic fibrosis is a clinically heterogeneous disorder. Especially the respiratory symptoms are significantly variable, even among patients with the same CFTR genotype. Therefore, there is an increasing interest in searching for the genetic modifiers of the clinical outcome in CF. This review presents the actual state of knowledge in terms of the potential genes-modifiers of the pulmonary form of cystic fibrosis.

Cystic Fibrosis↗

PubMedDate not supplied

[II. Pharmacogenetics--the future of modern pharmacology and genetics].

Pharmacogenetics is a scientific discipline connecting pharmacology and genetics. Its point of interest is an analysis of the variable, genetically determined patient's response to drugs. The basic discovery in this field was the elucidation of the heterogenic response of patients to the tuberculostatic drug -- isoniazid. The new era of searching for the molecular background of the variable drugs metabolism has begun after identification, in the 50's, of the polymorphic variants of NAT2 gene. It encodes for N-acetyltransferase 2, an isoniazid metabolizing enzyme. The key catalysts of the biotransformation reactions are cytochrome P450 isoenzymes. Identification of the polymorphic variants of genes encoding these enzymes enabled an explanation of the heterogenic drugs tolerance. The current knowledge shows that the genetic defects that are responsible for variable pharmacological response concern not only genes encoding the metabolising enzymes but also transporter proteins and drug receptors. Due to achievements of the molecular genetics and putting into practice the modern bioinformatic technics new pharmacological opportunities have been created. It becomes possible to predict the patient's individual reactions and needs, without the necessity of treatment by "trial and error". Pharmacogenetics will allow to implement personalized therapy leading to safer and more effective drugs usage. Identification of the individual metabolising paths will reduce patient's exposition to the side effects of many drugs. In spite of many financial and logistic limitations there are chances of introducing the pharmacogenetic analysis -- as an obligatory step -- to the phases II and III of clinical trials by 2020.

Cytochrome P-450 Enzyme System↗