Lege Artis Medicinae

[THE GENOMIC BACKGROUND OF ALLERGY]

SZALAI Csaba

MARCH 20, 2004

Lege Artis Medicinae - 2004;14(03)

[In this review we summarise the current results of the genomic investigation of allergic diseases. From the genetic point of view allergy is multifactorial, which means that the susceptibility to the disease is determined by the effect of one or more genes or the interactions between multiple genes and involves important nongenetic factors such as the environment for their expression. Among allergic diseases the genomic background of asthma was studied most thoroughly. Until now, using hundreds of DNA markers, located across all of the human chromosomes, 16 genome-wide screens for susceptibility genes for asthma or asthma related intermediate phenotypes in 12 different populations have been published and 20 chromosomal regions have been highlighted for further analysis. In genetic association studies more than 500 genes were identified as candidate genes for asthma. In this review, we selected those results which were consistently reported by several independent studies or appeared particularly important or interesting. According to the results of the human genome programs and association studies we discuss the possible roles of candidate genes found in these loci in the pathomechanism of allergy and atopy.]

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[Insulin resistance is defined as a state of subnormal biological response to normal quantity of insulin. This phenomenon was first described by Hinsworth and Kerr in 1939, however it has come to the centre of interest only in the last two decades. It is the central pathogenetic factor of type 2 diabetes and the more complex clinical entity of metabolic syndrome, consequently also referred to as insulin resistance syndrome. In the background of insulin resistance alterations of the adipose tissue can be observed which clinically means obesity in most of the cases, however, this issue cannot be simplified to obesity only as increase in adipose tissue growth may be beneficial in certain cases. Current article discusses the explanation of this paradox and the pathophysiologic link between adipose tissue and insulin resistance. It also reviews the therapeutic aspects of insulin resistance emphasizing the role of thiazolidinedione type drugs having recently joined the therapeutic palette.]

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[Migraine sufferers in Hungary present a major epidemiological challenge with about 12% of the population affected. Authors have reviewed an extensive body of internationally published literature relative to the 5-hydroxi-triptamin receptor agonists such as the triptans. While summarising most relevant data with a view to enable physicians to choose the most effective therapy for an individual, the article also discusses the prevailing questions of efficacy, tolerability and safety. For those patients with differential-diagnostic difficulties referrals should be made to the specialized 'headache centers' of neurological departments.]

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PONGRÁCZ Endre, TORDAI Attila, CSORNAI Márta, NAGY Zoltán

[Introduction - This is the first Hungarian paper on the insertion/deletion polymorphism of ACE gene in stroke patients. According to literature data, the role of this polymorphism is controversial in the pathogenesis of stroke. The aim was to study the prevalence of the polymorphism in healthy persons and in stroke patients. Patients and methods - Blood samples from 173 unrelated healthy donors and 253 stroke patients were investigated by polymerase chain reaction (PCR). Preivous stroke was documented by CT or MRI and CDS. A routine questionnaire was used to study previous vascular events and the risk profile of patients. Results - I/I allele was found in 20%, I/D 52% and D/D 28% in the healthy group. Prevalence of the pathologic D/D allele did not differ between healthy and patients group (28% and 27%, OR: 0.88, and in subgroup age under 50 years OR: 1.00). No correlation was found between D/D and conventional risk profile but a positiv correlation was found in young patients having D/D and hyperlipidemia (p<0.05) and hyperfibrinogenemia (p<0.05). D/D prevalence was found higher in patients with family anamnesis of myocardial infarction (p<0.05). Very low prevalence of D/D allele was found in cardiogen embolic group (p>0.05). Conclusions - The ACE polymorphism does not seem to be an independent risk factor for stroke. However, in young stroke patients with D/D allele, hyperlipidemia and/or hyperfibrinogenemia present very high risk for stroke.]

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[A NEW DISCIPLINE IN THE CENTER OF MEDICAL RESEARCH AND CLINICAL PRACTICE - THOUGHTS ON BIOINFORMATICS]

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[Bioinformatics is one of the most important element of genomic research revolutionising biomedical science. This review describes the phenomena of genomic variance and comparative genomics. Briefly, the review summarises the identification procedure of new genes and gene expression patterns highly important in diagnostics. Bioinformatic procedures make possible the rapid detection of pathogens and have principal role in molecular drug design technologies.]

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[Extensive research efforts based on principles of evidence-based medicine have helped lately to accumulate large amount of information on the risks to the fetus during pregnancy. As a result, the standpoints concerning risks to the fetus have become more precise in many respects. A number of earlier assumptions have been proven to be exaggerated or unfounded and the range of cases at risk has been narrowed down. This paper presents the most important data on potential risks to the fetus originating from hereditary factors, infections, maternal diseases, drugs, irradiation and special gestational anomalies. The data presented highlight the necessity of identifying the fetal damage during the pregnancy unequivocally, based exclusively on evidence of probative force and with realistic appraisal of the danger of any existent fetal damage.]

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[Heat-shock proteins, or stress proteins play important role in cellular survival owning to their protective function. Their highly conserved structure renders them ideal messengers of cellular stress response. One of the best known representative of these proteins is the 70 kDa heat-shock protein (Hsp70), there is increasing amount of data about the intraand extracellular functions of this stress protein. In the present review the regulation of hsp70 gene expression, and hsp70 polimorfisms, the possible impact of polymorphisms to certain diseases, and the multilevel relationship between Hsp70 and the immun response are discussed. The authors review the role of Hsp70 in anti-tumor immunity, and the presence of anti-Hsp70 antibodies and their possible association with certain diseases. Here they present some of their recent observations: they detected the presence of anti-Hsp70 antibodies in all adult sera and found no correlation between these antibody levels and the presence of severe coronary heart disease. Recently we also showed, that human Hsp70 can activate the classical pathway of complement system in vitro, by direct binding of the first complement C1q.]

Hypertension and nephrology

[Association between the genetic polymorphism of heat-shock protein 72 and pediatric kidney diseases]

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[Recurring urinary tract infections (UTI) in childhood may result in chronic- and end-stage-renal-disease (ESRD), which leads to the initiation of dialysis and renal transplantation (NTx). Heat shock protein (HSP) 72 protects the kidney, whereas it refolds destroyed proteins and cells, and helps regenerating the renal tissue. The HSPA1B (1267)G allele is associated with lower HSP72 expression. This study assesses the role of HSPA1B A(1267)G polymorphism using PCR-RFLP in 103 children treated because of recurrent UTI, 26 children after NTx and 235 healthy controls. Clinical data were also evaluated. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele occurred more frequently in the UTI (p=0.0001; CI: 1.378-2.68) and in the NTx (p=0.014; CI: 2.29-187.7) patient group than in the controls group, and were associated with a higher risk for scarring (p=0.012; CI: 0.33-1.00) and renal malformation (p=0.0072; CI: 1.623- 140.6). Our data indicate a relationship between the carrier status of HSPA1B (1267)G allele and the development of recurrent UTI and ESRD, raising further questions about the clinical and therapeutic relevance of these polymorphism.]