CYTOGENETIC ANALYSIS OF CHROMOSOMAL ABERRATIONS IN PEOPLE PROFESSIONALLY EXPOSED TO IONISING RADIATION

S obzirom na sve veću izloženost humane populacije različitim izvorima radijacije, potrebno je, posebice u osoba profesionalno izloženih zračenju, pratiti njezine učinke na organizam. U ovom smo radu prikazali važnost primjene analize strukturnih kromosomskih aberacija, koja je najpouzdaniji biološki pokazatelj izloženosti ionizirajućem zračenjuThe people who are professionally exposed to radiation need to be monitored for its somatic and genetic effects. In this paper we presented the method of the structural chromosomal analysis that is the best biological indicator of the exposure to radiatio

CYTOGENETIC ANALYSIS OF CHROMOSOMAL ABERRATIONS IN PEOPLE PROFESSIONALLY EXPOSED TO IONISING RADIATION

S obzirom na sve veću izloženost humane populacije različitim izvorima radijacije, potrebno je, posebice u osoba profesionalno izloženih zračenju, pratiti njezine učinke na organizam. U ovom smo radu prikazali važnost primjene analize strukturnih kromosomskih aberacija, koja je najpouzdaniji biološki pokazatelj izloženosti ionizirajućem zračenjuThe people who are professionally exposed to radiation need to be monitored for its somatic and genetic effects. In this paper we presented the method of the structural chromosomal analysis that is the best biological indicator of the exposure to radiatio

HEMOCHROMATOSIS GENE MUTATIONS IN PATIENTS WITH ELEVATED SERUM IRON

Cilj našeg istraživanja bio je ustanoviti učestalost C282Y i H63D mutacija u bolesnika s povišenim vrijednostima serumskog željeza različite etiologije. U istraživanje je bilo uključeno 105 bolesnika (84 muškarca i 21 žena) koji su podijeljeni u dvije skupine. U prvoj je skupini bilo 55 bolesnika s povišenim vrijednostima serumskog željeza, koji su prekomjerno konzumirali alkohol, a u drugoj 50 bolesnika s povišenim vrijednostima serumskog željeza nepoznate etiologije. Prisutnost mutacija u HFE genu ustanovili smo metodom lančane reakcije polimeraze (PCR) nakon koje je slijedila restrikcija s odgovarajućim restrikcijskim endonukleazama. Prema dobivenim rezultatima, frekvencije C282Y i H63D alela u skupini bolesnika koji su konzumirali alkohol, iznose 4,5% i 20,1%, a u bolesnika s povišenim vrijednostima serumskog željeza nepoznate etiologije 18,0% i 19,0%. Usporedbom učestalosti HFE alela i genotipova između navedenih skupina bolesnika utvrdili smo statistički značajnu razliku (p<0,05) u frekvenciji C282Y alela kao i u frekvenciji C282Y homozigota. Naši rezultati upućuju na to da je analiza mutacija HFE gena korisna u bolesnika s povišenim vrijednostima serumskog `eljeza, pogotovo kad nije jasno ima li bolesnik jetrenu bolest s povišenim vrijednostima serumskog željeza ili ima nasljednu hemokromatozu uz povišene nalaze jetrenih enzima.To study the role of hemochromatosis gene mutations in patients with elevated serum iron, we have analysed C282Y and H63D mutations of the HFE gene. The investigation included 105 patients (84 males and 21 females) divided in two groups: 55 active alcoholic individuals (49 males and 6 females) and 50 individuals (35 males and 15 females) with elevated serum iron of unknown etiology. The analysis of HFE gene mutations was performed using the PCR-RFLP method. According to our results C282Y and H63D allele frequencies were 4.54% and 20.09% in active alcoholics and 18.00% and 19.00% in the second group of patients without the history of alcohol consumption, respectively. Comparing the HFE allele and genotype frequencies between investigated groups statistically significant differences (p 0.05) were observed in the frequency of C282Y allele and the frequency of C282Y homozygotes. Our results suggest that the analysis of HFE mutations can be useful in patients with the elevated serum iron, especially in patients with unclear hereditary hemochromatosis or another liver disease, such as alcoholic liver diseas

HEMOCHROMATOSIS GENE MUTATIONS IN PATIENTS WITH ELEVATED SERUM IRON

Cilj našeg istraživanja bio je ustanoviti učestalost C282Y i H63D mutacija u bolesnika s povišenim vrijednostima serumskog željeza različite etiologije. U istraživanje je bilo uključeno 105 bolesnika (84 muškarca i 21 žena) koji su podijeljeni u dvije skupine. U prvoj je skupini bilo 55 bolesnika s povišenim vrijednostima serumskog željeza, koji su prekomjerno konzumirali alkohol, a u drugoj 50 bolesnika s povišenim vrijednostima serumskog željeza nepoznate etiologije. Prisutnost mutacija u HFE genu ustanovili smo metodom lančane reakcije polimeraze (PCR) nakon koje je slijedila restrikcija s odgovarajućim restrikcijskim endonukleazama. Prema dobivenim rezultatima, frekvencije C282Y i H63D alela u skupini bolesnika koji su konzumirali alkohol, iznose 4,5% i 20,1%, a u bolesnika s povišenim vrijednostima serumskog željeza nepoznate etiologije 18,0% i 19,0%. Usporedbom učestalosti HFE alela i genotipova između navedenih skupina bolesnika utvrdili smo statistički značajnu razliku (p<0,05) u frekvenciji C282Y alela kao i u frekvenciji C282Y homozigota. Naši rezultati upućuju na to da je analiza mutacija HFE gena korisna u bolesnika s povišenim vrijednostima serumskog `eljeza, pogotovo kad nije jasno ima li bolesnik jetrenu bolest s povišenim vrijednostima serumskog željeza ili ima nasljednu hemokromatozu uz povišene nalaze jetrenih enzima.To study the role of hemochromatosis gene mutations in patients with elevated serum iron, we have analysed C282Y and H63D mutations of the HFE gene. The investigation included 105 patients (84 males and 21 females) divided in two groups: 55 active alcoholic individuals (49 males and 6 females) and 50 individuals (35 males and 15 females) with elevated serum iron of unknown etiology. The analysis of HFE gene mutations was performed using the PCR-RFLP method. According to our results C282Y and H63D allele frequencies were 4.54% and 20.09% in active alcoholics and 18.00% and 19.00% in the second group of patients without the history of alcohol consumption, respectively. Comparing the HFE allele and genotype frequencies between investigated groups statistically significant differences (p 0.05) were observed in the frequency of C282Y allele and the frequency of C282Y homozygotes. Our results suggest that the analysis of HFE mutations can be useful in patients with the elevated serum iron, especially in patients with unclear hereditary hemochromatosis or another liver disease, such as alcoholic liver diseas

Genes and celiac disease

Celijakija je bolest poremećenog imunosnog odgovora potaknutog glutenom koja se javlja u genetički predisponiranih osoba. Svrha ovog rada je prikazati dosadašnje spoznaje iz genetike celijakije. Genska podloga celijakije vezana za lokus humanih leukocitnih antigena kao dominantnog genetičkog elementa detaljno je razjašnjena. No postoji i velik broj gena izvan ove regije koji pridonose etiopatogenezi bolesti, a samo su dijelom zajednički pojedinim bolesnicima, što upućuje na genetičku heterogenost bolesti. Uz to je opaženo da su mnogi od tih rizičnih lokusa u celijakiji zajednički s lokusima za druge autoimunosne bolesti. Značajan doprinos novim spoznajama daju recentne cjelogenomske asocijacijske studije, ali tek treba istražiti velik dio još i sad nepoznate heritabilnosti u celijakiji.Celiac disease is a chronic infl ammatory disease of the small intestine triggered by gluten intake, which occurs in genetically susceptible individuals. The purpose of this paper is to present recent fi ndings in the genetics of celiac disease. Genetic background of celiac disease related to human leukocyte antigen locus (HLA) as a dominant genetic element has been well described. However, the existence of a large number of non-HLA celiac disease genes, only partly shared by each individual patient, suggests genetic heterogeneity of the disease. In addition, it has been observed that many of these risk loci in celiac disease are common with the loci for other autoimmune diseases. A signifi cant contribution to our knowledge has been provided by recent genome-wide association studies, but great part of the still unknown heritability in celiac disease is yet to be explored in the future

HLA-DQA1 and HLADQB1 genes in celiac disease

Cilj: Utvrditi učestalost alela i genotipova HLA-DQA1 i HLA-DQB1 gena u oboljelih od celijakije, kao i njihov utjecaj na kliničku ekspresiju bolesti. Ispitanici i metode: U ispitivanje je uključeno 110 pacijenata (60 žena i 50 muškaraca) s dijagnosticiranom celijakijom prema revidiranim ESPGHAN kriterijima (The European Society for Pediatric Gastroenterology Hepatology and Nutrition) koji su klinički obrađeni na Klinici za internu medicinu i Klinici za pedijatriju KBC-a Rijeka. Genotipizacija HLA alela klase II u pacijenata izvršena je metodom lančane reakcije polimerazom (PCR, engl. Polymerase Chain Reaction) s alel specifičnim početnicama (engl. Sequence Specific Primer – SSP), pri čemu su korišteni komercijalni kitovi niske i srednje rezolucije GenoVision SSP. Rezultati: Svi pacijenti imali su barem jedan rizični HLA-DQA1 ili HLA–DQB1 alel. Homozigota za rizične HLA-DQB1 alele bilo je 36,3 %, a za HLA-DQA1 34,5 %. Genotipovi za HLA-DQ2 i/ili DQ8 heterodimere prisutni su u 92,7 % pacijenata. HLA-DQ2 prisutan je u 79,1 % pacijenata, a HLA-DQ8 u 20,9 %. Nije utvrđena značajna razlika (P 0.05) in the frequency of the HLA-DQ2 and/or HLA-DQ8 carriers depending on the type of celiac disease. An earlier diagnosis and greater incidence of other autoimmune diseases in homozygotes, compared to other genotypes, was observed. Conclusions: The results have shown that the presence of HLA-DQ2/DQ8 heterodimers in Croatian celiac patients is in range with the existing north-south gradient in European populations. HLA genotyping in celiac patients has explicit effects in clinical practice when setting up the diagnosis

4G/5G POLYMORPHISM IN PROMOTER REGION OF PLASMINOGEN ACTIVATOR INHIBITOR-1 GENE AS RISK FACTOR IN MULTIPLE SCLEROSIS

Da bi se ispitalo moguće značenje proteolitičkih mehanizama na razvoj upalnih lezija u MS-u, u radu je analiziran utjecaj polimorfizma 4G/5G u promotorskoj regiji gena za inhibitor aktivatora plazminogena- 1 (PAI-1) na podložnost za MS i kliničku ekspresiju bolesti. Ispitanici su bili bolesnici iz Gorkog kotara s klinički sigurnim i laboratorijski potvr|đenim sigurnim MS-om (N=46), a u kontrolnoj su skupini bili dobrovoljni davatelji krvi, autohtoni stanovnici iz istog područja (N=101). Rezultati su pokazali da se distribucija PAI-1 genotipova i alela u MS-bolesnika nije statistički razlikovala od učestalosti u zdravih ispitanika, a razlike nije bilo niti kada su uspore|đeni pojedini subtipovi bolesti (PP, SP i RR) međ|usobno kao i sa zdravim ispitanicima. Nije bilo ni statistički značajne razlike u dobi nastupa i progresiji bolesti izme|đu pojedinih PAI-1 genotipova. Stoga možemo zaključiti da polimorfizam 4G/5G PAI-1 gena nema utjecaja na podložnost kao ni na ekspresiju bolesti u MS-bolesnika iz Gorskog kotaraIn view of the potential importance of the proteolytic mechanisms in the development of MS lesions, the authors studied whether the 4G/5G promoter polymorphism of the plasminogen activator inhibitor 1 (PAI 1) gene may play a role in the clinical characteristics of Gorski kotar MS patients and their potential genetic susceptibility to MS. A total of 46 patients with clinically definite and laboratory supported MS were recruited from Gorski kotar region, while the control group consisted of 101 unrelated ethnically matched healthy blood donors. The distribution of PAI-1 genotypes and alleles in MS patients was similar to the distribution pattern in healthy donors. Furthermore, no association was observed between the PAI-1 promoter polymorphism and clinical characteristics, such as clinical course, age of disease onset and disease progression. Therefore, we can conclude that the 4G/5G promoter polymorphism of the PAI-1 gene does not influence the susceptibility to MS or the clinical characteristics of MS in Gorski kotar patients

4G/5G POLYMORPHISM IN PROMOTER REGION OF PLASMINOGEN ACTIVATOR INHIBITOR-1 GENE AS RISK FACTOR IN MULTIPLE SCLEROSIS

Da bi se ispitalo moguće značenje proteolitičkih mehanizama na razvoj upalnih lezija u MS-u, u radu je analiziran utjecaj polimorfizma 4G/5G u promotorskoj regiji gena za inhibitor aktivatora plazminogena- 1 (PAI-1) na podložnost za MS i kliničku ekspresiju bolesti. Ispitanici su bili bolesnici iz Gorkog kotara s klinički sigurnim i laboratorijski potvr|đenim sigurnim MS-om (N=46), a u kontrolnoj su skupini bili dobrovoljni davatelji krvi, autohtoni stanovnici iz istog područja (N=101). Rezultati su pokazali da se distribucija PAI-1 genotipova i alela u MS-bolesnika nije statistički razlikovala od učestalosti u zdravih ispitanika, a razlike nije bilo niti kada su uspore|đeni pojedini subtipovi bolesti (PP, SP i RR) međ|usobno kao i sa zdravim ispitanicima. Nije bilo ni statistički značajne razlike u dobi nastupa i progresiji bolesti izme|đu pojedinih PAI-1 genotipova. Stoga možemo zaključiti da polimorfizam 4G/5G PAI-1 gena nema utjecaja na podložnost kao ni na ekspresiju bolesti u MS-bolesnika iz Gorskog kotaraIn view of the potential importance of the proteolytic mechanisms in the development of MS lesions, the authors studied whether the 4G/5G promoter polymorphism of the plasminogen activator inhibitor 1 (PAI 1) gene may play a role in the clinical characteristics of Gorski kotar MS patients and their potential genetic susceptibility to MS. A total of 46 patients with clinically definite and laboratory supported MS were recruited from Gorski kotar region, while the control group consisted of 101 unrelated ethnically matched healthy blood donors. The distribution of PAI-1 genotypes and alleles in MS patients was similar to the distribution pattern in healthy donors. Furthermore, no association was observed between the PAI-1 promoter polymorphism and clinical characteristics, such as clinical course, age of disease onset and disease progression. Therefore, we can conclude that the 4G/5G promoter polymorphism of the PAI-1 gene does not influence the susceptibility to MS or the clinical characteristics of MS in Gorski kotar patients

The Role of Iron and Iron Overload in Chronic Liver Disease

The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models

Tumor Necrosis Factor-alpha-308 Gene Polymorphism in Croatian and Slovenian Multiple Sclerosis Patients

Previous findings regarding the role of TNF-a-308 gene polymorphism in multiple sclerosis (MS) are contradictory.This study's aim was to investigate the possible influence of TNF-a-308 polymorphism on MS susceptibility and MS disease process in a Croatian and Slovenian population. Genotyping was performed in 338 patients and 460 healthy controls. The TNF2 allele was present in 123 (26.8%) of healthy controls versus 67 (19.9%) of MS patients (p=0.023, odds ratio=0.68, 95% confidence interval=0.48-0.95), suggesting that carriage of the TNF2 allele might decrease MS risk. The difference of TNF2-allele carrier frequency between patients and controls was identified in relapsing-remitting (RR) MS group.There was no association between TNF2-allele carrier status and age at disease onset or disease progression. Our results suggest that in the study populations the TNF-a-308 polymorphism may play a role in MS susceptibility