[Prevalence of the Diabetic Retinopathy and Genetic Factors Significance in the Development of Diabetic Retinopathy in Patients with Diabetes Mellitus type I and II in Slovakia (DIARET SK study). Overview of Actual Findings and Design of the Epidemiological DIARET SK Study]. / Prevalencia DIAbetickej RETinopatie a význam genetických faktorov v rozvoji diabetickej retinopatie u pacientov s diabetes mellitus typu 1. a 2. na Slovensku (DIARET SK). Prehlad aktuálnych poznatkov a postavenie epidemiologickej stúdie DIARET SK.

INTRODUCTION: Diabetic retinopathy (DR) is the second most common microvascular complication and the most common cause of blindness in patients with diabetes mellitus (DM). Despite the ongoing research, the findings of diabetic retinopathy epidemiological and risk factors are, until now, not consistent. More finding may be revealed by epidemiological studies, consistently mapping DR epidemiology under the current possibilities of investigations and treatment of the DM. DIARET SK: DIARET SK Study, with 5 000 enrolled patients with diabetes mellitus in the Slovak Republic, is, until now, the largest epidemiological study to set the prevalence of diabetic retinopathy. The primary aim is to establish the prevalence of diabetic retinopathy in patients with diabetes mellitus type I and II, according to the duration of the disease. The secondary aim is to establish prevalence of the different stages of the DR and diabetic macular edema (DME) and analysis of the risk factors influence. Included are patients with DM type I and II regardless to the ocular complications history and the period of DM duration. Each enrolled patient has both complex diabetic and ophthalmic examinations.Projects to establish DR prevalence: Tens of projects concerned with diabetic retinopathy epidemiology with different approaches to establish the prevalence and with different patients population. Results from different studies vary significantly (from 12.3 % to 66.9 %). The results depend on the design of the study and the patients recruitment, used examination methods, specific patients population with regard to the geography, prevalence of risk factors, period of diabetes duration, glycated hemoglobin (HbA1C) level, blood pressure, and is higher in type I diabetic patients. The most accurate results are from population epidemiological studies with well-controlled patient recruitment and uniform complex examination that are similar to the DIARET SK study. CONCLUSION: The DIARET SK study represents the largest epidemiological study to establish the prevalence of the diabetic retinopathy in patients with DM type I and II. Thanks to the quality design, similar to the already published studies, but with larger number of patients and newest examinations methods, the DIARET SK study has the aspiration to obtain the most accurate up to date data of diabetic retinopathy prevalence and risk factors influence to its outbreak. The patients recruitment started in February 2015. The expected date of patients recruitment termination is in the end of the year 2015, and the data analysis in 2016.

Lack of association between chronic periodontitis and the Toll-like receptor 4 gene polymorphisms in a Czech population.

BACKGROUND AND OBJECTIVE: Periodontitis is a bacterially induced chronic inflammatory disease and a major cause of tooth loss among adults. Toll-like receptors are signal molecules essential for the cellular response to bacterial cell wall components. The aim of this study was to investigate relationships between chronic periodontitis and variations in the TLR4 gene. MATERIAL AND METHODS: A total of 171 patients with chronic periodontitis and 218 unrelated controls were genotyped for the Asp299Gly (896A>G) and Thr399Ile (1196C>T) polymorphisms of the TLR4 gene. RESULTS: Both variants were in nearly complete linkage disequilibrium. No homozygotes for the less common alleles, 299Gly and 399Thr, respectively, were found. The prevalence of the Asp299Gly and the Thr399Ile heterozygotes was 5.3% and 5.0% in controls, and 7.0% and 7.0% in periodontitis patients. CONCLUSION: In conclusion, TLR4 gene polymorphisms were not significantly associated with the susceptibility to, or severity of, chronic periodontitis in our population.

Neuronal nitric oxide synthase gene polymorphism and IgE-mediated allergy in the Central European population.

BACKGROUND: Several findings suggest that nitric oxide (NO) plays a significant role in the regulation of the Th1/Th2 balance and contributes to the development of allergic diseases. Our study investigates a possible association of C/T transition located 276-bp downstream from the translation termination site in exon 29 of the human nitric oxide synthase type 1 (NOS1) gene with immunoglobulin E (IgE)-mediated allergic diseases in the Czech population. METHODS: The study included 688 subjects - 368 patients with clinically manifested allergic diseases and 320 unrelated controls with negative familial history of asthma/atopy. The NOS1 genotypes were determined by polymerase chain reaction (PCR) and restriction analysis by Eco72I. RESULTS: No significant differences were found for allele or genotype frequencies of the 5266 C/T polymorphism in exon 29 of the NOS1 gene between IgE-mediated allergic diseases (or asthma alone) and healthy subjects. However, this common polymorphism showed a significant association with signs of atopy, especially with total serum IgE levels [log(e) IgE levels (mean +/- SD): CC genotype = 4.34 +/- 1.40; CT genotype = 4.58 +/- 1.53; TT genotype = 5.01 +/- 1.61; P < 0.05). CONCLUSIONS: Our findings suggest that NOS1 gene may participate in the pathogenesis of high total serum IgE levels in allergic diseases in our population. These findings provide support for NOS1 as a candidate gene for IgE-mediated allergy.

Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE-mediated allergy.

BACKGROUND: Immunoglobulin E (IgE)-mediated allergy belongs to common chronic disorders resulting from an interaction between both genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31.1, a region that is linked to asthma and bronchial hyperresponsiveness. Recently, several polymorphisms in the promoter region of this gene have been associated with atopic phenotypes in various populations. METHODS: We investigated relationship among atopic phenotypes and two polymorphisms [C(-159)T and G(-1359)T] in the promoter of the CD14 gene in the Czech population. Polymerase chain reaction with restriction fragment length polymorphism analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n = 562) and random controls (n = 320). RESULTS: The CD14 allele or genotype distributions were similar in patients and control group. However, the frequency of the C allele of the C(-159)T polymorphism was higher in patients with positive skin prick tests for moulds than in patients without reactivity to this antigen (P < 0.002, Pcorr<0.01). In addition, we found that patients with homozygous genotype (GG) of the G(-1359)T polymorphism had marginally lower percentage of positive skin prick tests compared with the other genotypes (P < 0.029, Pcorr > 0.05). CONCLUSIONS: Our study supports the idea that CD14 gene variants may act as disease modifiers of IgE-mediated allergic diseases.

Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma.

BACKGROUND: Asthma is a common multifactorial disease, the aetiology of which is attributable to both environmental and genetic factors. The endothelial nitric oxide synthase (NOS3) gene has been implicated in asthma pathogenesis. OBJECTIVE: This study investigated associations of 27 base-pair tandem repeat polymorphism in intron 4 and the Glu298Asp (G894T) variant of the NOS3 gene with atopic asthma in a Czech population. METHODS: Polymerase chain reaction was used to determine the NOS3 genotypes in subjects with atopic asthma (n = 163) and random controls (n = 209). RESULTS: The NOS3 allele or genotype distributions did not differ significantly between the control and asthma groups. However, the common genotype (bb) of the NOS3 polymorphism in intron 4 was found to be significantly associated with total IgE levels (P = 0.006), specific IgE levels for feathers (P = 0.0002) and a positive skin prick test for hay (P = 0.004). In one atopic patient, we identified an additional 27-bp repeat in the NOS3 gene (NOS3c), which occurred in heterozygous combination with the NOS3b allele (NOS3b/c genotype). In addition, we describe a new polymorphism (A5495G) in the NOS3 gene, which was in almost complete linkage disequilibrium with the NOS3 repeat polymorphism in intron 4. The Glu298Asp variant was not associated with asthma and/or related atopic phenotypes in our study. CONCLUSION: Neither the NOS3 'b' allele nor the NOS3 'b/b' genotype showed any general association with atopic asthma, but they were associated with atopy-related phenotypes. We conclude that the NOS3 gene polymorphisms may act as disease modifiers in atopic asthma phenotype in our population.

Plasminogen-activator-inhibitor-1 promoter polymorphism as a risk factor for adult periodontitis in non-smokers.

Periodontal diseases belong to the most common chronic disorders affecting mankind. Smoking and impaired plasminogen activation with hypercoagulation and fibrinolysis inhibition have been proposed as having a role in predisposition to these diseases. We investigated relationships among adult periodontitis, smoking, and a variation in the deletion/insertion (4G/5G) promoter polymorphism of the plasminogen-activator-inhibitor-1 (PAI-1) gene in 304 Caucasian subjects. An association was detected between the deletion (4G) allele (and 4G/4G genotype) and periodontitis (P = 0.0022, P(corr) < 0.01; P = 0.014, P(corr) < 0.05). A stronger association occurred in non-smokers (P = 0.00021, P(corr) < 0.01; P = 0.0024, P(corr) < 0.05) where the presence of the PAI-1 gene 4G allele appears to be one of the risk factors for periodontitis.

Polymorphism 4G/5G in the plasminogen activator inhibitor-1 (PAI-1) gene is associated with IgE-mediated allergic diseases and asthma in the Czech population.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is a glycoprotein that belongs to the serine protease inhibitor superfamily and has an essential role in tissue remodeling after inflammation. Recently, a single base pair deletion/insertion (4G/5G) polymorphism of the PAI-1 gene has been associated with an increased risk of asthma in nuclear families from the UK. METHODS: The present study was thus conducted to determine the association of this polymorphism with the development of IgE-mediated asthma and other allergic diseases in the Czech population. A case-control approach was used in our study. DNA taken from subjects with clinically manifested asthma and other allergic diseases (n = 207) and from reference ethnically age-gender-matched unrelated subjects (n = 186) was examined for base deletions/insertions in the PAI-1 gene. RESULTS: A significant association (P = 0.0035) was observed between the PAI-1 promoter polymorphism and IgE-mediated allergic diseases altogether. Furthermore, the 4G allele frequency was also significantly higher in the asthmatic patients than in the control group (P = 0.0148). CONCLUSIONS: Our findings support the idea that the 4G allele of the 4G/5G polymorphism in the PAI-1 gene may be a risk factor for IgE-mediated asthma and allergic diseases.

Distribution of the receptor for advanced glycation end products gene polymorphisms in patients with chronic periodontitis: a preliminary study.

BACKGROUND: Periodontal diseases are viewed today as multifactorial problems initiated and sustained by bacteria but significantly modified by the body's response to bacterial plaque. A recent study suggested that receptor for advanced glycation end products (RAGE) could be involved in the pathophysiology of periodontitis. The aim of this study was to investigate a possible association of 3 common polymorphisms in the RAGE gene with chronic periodontitis. METHODS: We studied 101 Caucasian patients with chronic periodontitis together with 162 orally healthy subjects. Three polymorphisms, one in intron 7 (1704G/T), second in intron 8 (2184A/G), and the third in exon 3 (G82S) of the RAGE gene, were investigated by polymerase chain reaction methods (PCR) with subsequent enzymatic restriction with Bfal, BsmFI, or Alu Il, respectively. RESULTS: A statistically significant difference in allele frequencies between patients and the reference group was found for intron variant 1704G/T (P= 0.02, Pcorr >0.05). There was no significant difference in genotype or allele frequency distributions between groups for intron variant 2184A/G or for the exon variant exchanging amino acid Gly for Ser at position 82 (G82S). CONCLUSIONS: We can speculate that susceptibility to the development of chronic periodontitis could be influenced by the 1704G/T polymorphism of the RAGE gene, independently of diabetes.