Lydie IzakovičováHollá

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach.

Aims/hypothesisIn the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single- and multi-locus analyses.Materials and methodsThe study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCR-based methodology (PCR only, PCR plus RFLP, or allele-specific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis.ResultsAfter correction for multiple comparisons, only one SNP, in the gene encoding the receptor of advanced glycation end products, AGER 2184A/G (gene symbol formerly known as RAGE) showed a significant association with DN (p = 0.0006) in single-locus analysis. In multi-locus analysis, six SNPs exhibited a significant association with DN: four SNPs on chromosome 6p (AGER 2184A/G, LTA 252A/G, EDN1 8002G/A and AGER -429T/C) and two SNPs on chromosome 7q (NOS3 774C/T and NOS3 E298D), omnibus p = 0.033. Haplotype analysis revealed significant differences between DN and control groups in haplotype frequencies on chromosome 6 (p = 0.0002); however, there were no significant difference in the frequencies of the NOS3 haplotypes on chromosome 7. Logistic regression analysis identified SNPs AGER 2184A/G and NOS3 774C/T, together with diabetes duration and HbA1c, as significant predictors of DN. Testing for interactions between SNPs on chromosomes 6 and 7 did not provide significant evidence for epistatic interaction.Conclusions/interpretationUsing the set-association approach we identified significant associations of several SNPs on chromosomes 6 and 7 with DN. The single- and multi-locus analyses represent complementary methods.

C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer.

BackgroundLow-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of LRP1 is related to invasiveness of cancer cells. However, recent data on LRP1 suggest that this receptor can also be involved in tumor establishment and progression.MethodsWe investigated an association between the C766T polymorphism of the third exon of the LRP1 gene and breast cancer in a sample of women of Caucasian origin. Allele and genotype frequencies of this polymorphism were assessed in 164 women with breast cancer and in 183 age-compatible women without a history of any cancer disease.ResultsAn increase in LRP1 T allele frequency in subjects with breast cancer was observed compared with controls (0.21 versus 0.15, P = 0.01963). A significant excess of genotypes with the T allele (homozygotes plus heterozygotes) was also observed (odds ratio 1.743, 95% confidence interval 1.112–2.732).ConclusionThe T allele of the C766T polymorphism in the LRP1 gene is associated with an increased risk of breast cancer development in women of Caucasian origin.

Interleukin-18 and its three gene polymorphisms relating to allergic rhinitis.

AbstractThe study aimed to examine an association of three different single nucleotide polymorphisms (SNPs) of the IL-18 gene (−607 C/A, −137 G/C and −133 C/G) on chromosome 11q22 with allergic rhinitis (AR). Genotyping for the SNPs was performed using 539 patients with AR and 312 healthy control volunteers. Positivity to the skin prick test for the fungus Alternaria sp. in patients with AR, and IgE levels according to particular genotypes of selected SNPs, were also determined. There were no significant differences in the distribution of single IL-18 alleles or genotypes between controls and AR patients. However, frequencies of combined IL-18 genotypes arising from combinations of the three common polymorphisms (−607, −137 and −133) were significantly different between both groups (P = 0.009, Pcorr < 0.05, OR = 5.35, 95% CI: 1.9–15.2). There was a marginally significant association of the IL-18–607 variant with IgE levels (P = 0.05) in patients, but not in the case of the other SNPs. Patients allergic to Alternaria, but not those allergic to other antigens, showed a significant association with the IL-18–607 polymorphism (P = 0.0037, Pcorr < 0.05). Results suggest that IL-18 gene variants may be one of the factors participating in the pathogenesis of AR or its intermediary phenotypes.

Root resorption associated with ectopically erupting maxillary permanent canines: a computed tomography study

The aims of this retrospective computed tomography (CT) study were to determine the occurrence of severe root resorption involving the pulpal canal of adjacent permanent teeth associated with ectopically erupting canines, and to verify the existence of related factors. The sample consisted of 255 consecutive patients (159 females and 96 males, mean age 18.4 and 16.8 years, respectively). Three hundred and thirty-four ectopic maxillary canines and adjacent teeth were analysed using CT images. Statistical significance was evaluated with chi-square and Fishers exact tests. The results showed that severe root resorption of adjacent permanent teeth occurred in 17.7 per cent of ectopic canines and was equally common in females and males. Severe root resorption affected 12.6 per cent of the lateral incisors, 4.8 per cent of the first premolars, and 2.1 per cent of the central incisors. No relationship was found between the type or side of ectopic eruption, inclination of the longitudinal axis of the ectopic canine and the occurrence of severe root resorption. A significant relationship was found between a bucco-lingual position of the ectopic canine and root resorption (P < 0.05). Root resorption mainly occurred in the apical third (57.6 per cent) and apical and middle thirds (27.1 per cent). A significant relationship existed between the occurrence of root resorption and complete loss of space for the erupting canine (P < 0.05). No association was found between alignment of the upper permanent incisor and root resorption. A widened dental follicle occurred in 15 per cent of ectopic canines but did not cause root resorption of the adjacent permanent teeth. Since root resorption is asymptomatic, early detection by radiographic examination is essential for correct diagnosis and treatment.

Relationship of age and the body mass index to selected hypertensive complications in pregnancy.

Objectives: Older maternal age is considered to be a risk factor for a number of pregnancy‐associated pathologies. Average weight increases with age. The aim of this study is to assess the effects of maternal age on selected disorders of pregnancy independently from the influence of maternal weight. Methods: The retrospective study included 910 women. The following parameters were evaluated: age, p‐BMI (body mass index before pregnancy), hypertension, severe hypertension, pre‐eclampsia, proteinuria, severe proteinuria, thromboembolic diseases, pregnancy duration and fetal growth restriction. Results: The correlation between the p‐BMI and age and BMI was confirmed (P<0.001). After filtering away the mutual influence of age and p‐BMI applying logistic regression we proved a statistically significant effect of p‐BMI on the incidence of hypertension, severe hypertension, proteinuria and pre‐eclampsia (P<0.001). The maternal age (cleared of the p‐BMI) effects only hypertension. Conclusions: Age alone proved to be a risk factor for severe hypertension or severe hypertension of the pregnant subjects. Increased risk for proteinuria, hypertension and pre‐eclampsia is directly associated with p‐BMI of the pregnant women, and only indirectly with their age.

Lack of an Association of a Single Nucleotide Polymorphism in the Promoter of the Matrix Metalloproteinase-1 Gene in Czech Women with Pregnancy-Induced Hypertension.

In preeclampsia the cytotrophoblast invasion of the decidual vessels is reduced. The endothelia in the decidual vessels may influence cytotrophoblast invasion and remodeling of decidual spiral arteries. The decidual endothelial cells from preeclamptic placentas produce less matrix metalloproteinase-1 (MMP1) than those from normal placentas. MMPs form a group of enzymes that are capable of degrading components of extracellular matrix. The present study investigated the prevalence and possible association of an insertion of guanine in the promoter of the MMP1 gene in pregnancy-induced hypertension, preeclampsia and eclampsia in the Czech population. This was a case-control study. No differences were observed in genotype frequencies between cases and controls. The insertion of the guanine in the promoter of the MMP1 gene does not appear to increase the risk of development of pregnancy-induced hypertension, preeclampsia and eclampsia.

I/D ACE gene polymorphism in survival of leukemia patients -- hypothesis and pilot study.

Angiotensin-I converting enzyme (ACE) is involved not only in intracellular volume regulation but also in proliferation control. Since both ACE gene polymorphism (I/D ACE) and ABO blood group determine ACE level in peripheral blood and probably also in bone marrow, the hypothesis to the interindividual differences in survival of leukemic patients was suggested. The data of 25 patients of both sexes with acute myelogenous (AML), acute lymphatic (ALL), chronic myelogenous (CML) and chronic lymphatic (CLL) leukemia treated by conventional were used for the study. The overall survival (SUR) was estimated as the time from the date of diagnosis to the date of death. The difference between patients individual SUR (iSUR) and median SUR according to the type of leukemia (mSUR) was calculated. This difference (iSUR-mSUR) varied with I/D ACE genotype (p<0.02) but neither with diagnosis nor with ABO blood group. The regression model for iSUR calculation, from mSUR and I/D ACE genotype, has been suggested.

Polymorphisms in HLA-related genes and psoriasis heredity in patients with psoriasis

The aim of this study was to investigate possible associations of the five DNA polymorphic genotypes in the HLA region (transporter associated with antigen processing [TAP1; TAP1 333 a/b, TAP1 637 c/d], the HLA‐DRB1*1501‐rs3135388, tumor necrosis factor [TNF]α [−238 G/A] and NcoI TNFβ) with characteristics of family history in patients with psoriasis vulgaris.

Association of Single Nucleotide Polymorphisms in the Eosinophil Peroxidase Gene with Allergic Rhinitis in the Czech Population

Background: Eosinophil peroxidase (EPO) gene codes a cationic protein released from the specific granules of activated eosinophils. Eosinophil granulocytes play a central role in the protection of organisms against parasites. They are also regarded as key effector cells in allergic inflammation. We attempted to determine the polymorphisms in the EPO gene typical for the Czech population and to analyze their associations with allergic rhinitis and its intermediary phenotypes. Methods: We sequenced all 12 exons of the EPO gene, and selected variants were subsequently analyzed by polymerase chain reaction and restriction fragment length polymorphism methods in a case-control study comprising a total of 613 subjects (319 controls and 294 patients with rhinitis). Results: In total, 5 polymorphisms (–1710T/C and –1710T/CTCC, 2649T/C, 3097A/G and 3979A/G) were found in the EPO gene. Polymorphisms 2649T/C and 3097A/G were in complete linkage disequilibrium (D′ = 1 for both groups), and both of them were in a strong disequilibrium with the 3979A/G variant (D′ = 0.801 for controls, D′ = 0.848 for rhinitics). Consequently, these 3 polymorphisms were studied in association with the allergic phenotype. In a single locus analysis, only 3979A/G single nucleotide polymorphism was marginally significantly associated with rhinitis (p = 0.030, pcorr > 0.05). This polymorphism also showed a marginal association with total serum IgE levels (loge IgE, mean ± SD: genotypes GG = 2.60 ± 1.20; GA = 2.47 ± 1.88; AA = 2.38 ± 1.49; p < 0.05). Furthermore, significant differences in haplotype frequencies between patients and healthy subjects were observed (p < 0.05). Conclusions: Our study supports the hypothesis that genetic variability in the EPO gene may contribute to the susceptibility to allergic rhinitis (or related phenotypes) in the Czech population.

Dentoskeletal characteristics in patients with palatally and buccally displaced maxillary permanent canines

The aim of this retrospective study was to analyse dentoskeletal characteristics in patients with eruption disturbances of the maxillary permanent canines. Pre-treatment panoramic radiographs and lateral cephalograms of 636 consecutive orthodontic patients were assessed. The control group included 456 patients with physiologically erupted maxillary permanent canines (261 females and 195 males, mean age 12.6 and 12.4 years, respectively). The other groups comprised 144 subjects with palatally displaced canines (PDCs) (92 females and 52 males, mean age 14.2 and 14.7 years, respectively) and 36 patients with buccally displaced canines (BDCs) (16 females and 20 males, mean age 12.4 and 12.8 years, respectively). The selected dentoskeletal parameters were compared with classic cephalometric norms using the method of analysis of variance, chi-square, and Fishers exact tests. The PDC patients showed a significantly more prognathic maxilla, a significantly more frequent occurrence of skeletal class I, retroinclination of maxillary central incisors, hypodivergent relationship, and mandibular anteriorotation and less frequent posteriorotation. A significantly more frequent retrognathic maxilla and skeletal class III and less frequent retroinclination of the maxillary central incisors were found in the BDC patients. The results of this study indicate the existence of different facial morphology and more likely also etiopathogenesis of eruption disturbances of the canines in the PDC and BDC patients.