• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

The association between gene variant rs7635818 located on chromosome 3p12.3 and abdominal aortic aneurysm (AAA) was not unambiguously determined by the results of genome-wide association studies. The aim of our study was to examine this possible association in the Slovak population, with respect to the presence and severity of AAA.A cross-sectional study was conducted between August 2016 and March 2020. The study included 329 participans, 166 AAA patients and a control group of 163 subjects without confirmed AAA with comparable distribution of genders. The anteroposterior diameter of the abdominal aorta was determined by duplex ultrasonography. AAA was defined as subrenal aortic diameter ≥ 30 mm. DNA samples were genotyped using real-time polymerase chain reaction and subsequent high-resolution melting analysis in presence of unlabelled probe. Genetic models studying the possible association were adjusted to age, sex, smoking, arterial hypertension, diabetes mellitus, creatinine and body mass index (BMI) in multivariate analysis. In the additive model, presence of each C-allele of rs7635818 polymorphism was associated with an almost 50 % increase in probability of developing AAA (OR 1.49; 95 % CI 1.06-2.08; p=0.020). Compared to GG homozygotes, CC homozygotes had more than two times higher risk of developing AAA (OR 2.23; 95 % CI 1.14-4.39; p=0.020). The risk of AAA was also in the recessive model higher for CC homozygotes compared to G-allele carriers (GC/GG) (OR 1.79; 95 % CI 1.01-3.19; p=0.047).The abdominal aortic diameter in CC homozygotes of the rs7635818 polymorphism was 7.66 mm greater compared to GG homozygotes (42.5±22.0 mm vs 34.8±21.3 mm; p=0.022) and 5.88 mm greater compared to G-allele carriers (GC/GG) (42.5±22.0 mm vs 36.6±21.0 mm; p=0.04) in univariate analysis. C-allele variant in rs7635818 G>C polymorphism is associated with a higher probability of developing AAA in the Slovak population.

• MeSH
• aneurysma břišní aorty diagnostické zobrazování   etnologie   genetika   MeSH
• běloši genetika   MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• hodnocení rizik MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 3 * MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Aim: We examined associations of eight SNPs in/near seven candidate genes with glycemic response to 6 month treatment with DPP4 inhibitors. Patients & methods: 206 patients with type 2 diabetes (116 men and 90 women) were treated with sitagliptin or vildagliptin (both 100 mg/day) in combination with metformin or metformin/sulphonylurea over 6 months, and the reduction in glycated hemoglobin (HbA1c) was measured. Results: Rs6923761 in GLP1R was significantly associated with a reduction in HbA1c (adjusted p = 0.006). Homozygotes for the minor A allele had smaller reduction in HbA1c by 0.4% (4 mmol/mol) than the G allele carriers (p = 0.016). Conclusion: The missense variant rs6923761 in the GLP1R gene was associated with a smaller glycemic response to 6 month gliptin therapy in diabetic patients of central European origin.

• MeSH
• alely MeSH
• diabetes mellitus 2. typu * farmakoterapie   genetika   MeSH
• inhibitory dipeptidylpeptidasy 4 * terapeutické užití   MeSH
• lidé MeSH
• metformin * MeSH
• vildagliptin terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Only afew gene variants were associated with the response to dipeptidylpeptidase-4 inhibitors (DPP4I). KCNQ1 gene variants were previously related both to type 2 diabetes (T2D) and incretin effect. We hypothesized that T2D related KCNQ1 variants would be associated with smaller glucose-lowering effect of DDP4I. METHODS: We performed a retrospective study in 137 Caucasian subjects with T2D who were followed for 6months after initiation of DPP4I treatment. Genotyping for KCNQ1 rs163184 and rs151290 was performed using PCR-HRMA and PCR-RFLP methods, respectively. The main clinical outcome was reduction in HbA1c (ΔHbA1c) after 6-month DPP4I treatment. RESULTS: KCNQ1 rs163184 T>G variant was associated with the response to DPP4I treatment in genetic additive model (β=-0.30, p=0.022). For each G allele in the rs163184 genotype, we observed a 0.3% (3.3mmol/mol) less reduction in HbA1c during treatment with a DPP4I. Both the GG homozygotes and G-allele carriers had significantly smaller HbA1c reduction in comparison with the TT homozygotes. CONCLUSIONS: KCNQ1 rs163184 T>G variant was associated with a reduced glycaemic response to DPP4I. The difference of 0.6% (6.5mmol/mol) in HbA1c reduction between the TT and GG homozygotes might be of clinical significance if replicated in further studies.

• MeSH
• alely MeSH
• diabetes mellitus 2. typu farmakoterapie   genetika   MeSH
• draslíkový kanál KCNQ1 genetika   MeSH
• genotyp MeSH
• glykovaný hemoglobin analýza   MeSH
• inhibitory dipeptidylpeptidasy 4 terapeutické užití   MeSH
• krevní glukóza analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický genetika   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Východiská: Cieľom pilotnej štúdie bolo zistiť, či expresiu génov pre UP-II a EGFR RT-PCR a imunohistochemicky (IH) na vzorkách odobratých pred a po operácii možno využiť ako potenciálny nádorový marker na detekciu cirkulujúcich nádorových buniek (CNB) v periférnej krvi pacientov s TCC a výsledky porovnať so štandardným histopatologickým vyšetrením. Materiál a metódy: 43 pacientov (33 mužov a 10 žien) s TCC o vo veku 37–85 rokov, priemer 65 ± 12 rokov. Z nich 40 (93 %) malo TCC močového mechúra, 2 (4,6 %) TCC obličkovej panvičky a 1 (2,3 %) TCC močového mechúra, močovodu a obličkovej panvičky. V rámci štúdie bolo odobratých 10 ml periférnej krvi pacientov pred a do 1 hod po operácii, imunomagneticky separované CNB a určená expresia génov EGFR a UP-II pomocou RT-PCR. Následne bolo histopatologicky vyšetrené TCC tkanivo, určená endolymfatická, intravaskulárna a perineurálna invázia, expresia CK-7, CK-20, stromelysinu, Ki-67, p 53. IH bola vykonané aj na vzorkách separovanej krvi pred a po operácii na prítomnosť CNB farbením hematoxylínom-eozínom (HE) a podľa Papanicolaua (PAP), ako aj na prítomnosť expresie CK-7, CK-20. Výsledky: EGFR a UP-II boli exprimované u 24 z 35 (68,6 %) a u 19 z 35 (54,3 %) vzoriek TCC tkaniva. EGFR nebol exprimovaný v žiadnej vzorke krvi ani imuno-separovaných buniek. UP-II bol exprimovaný v 1 z 19 (5,3 %) vzoriek imuno-separovaných CNB získaných pred operáciou, ale v žiadnej vzorke imuno-separovaných CNB získaných po operácii (P < 0,9999). Expresia UP-II bola detegovaná v 2 z 32 (6,3 %) vzoriek krvi odobratých pred operáciou a v 3 z 32 (9,4 %) vzoriek krvi odobratých do jednej hodiny po operačnom zákroku (P < 0,9999). U 11 zo 43 (25,6 %) pacientov sa pri histopatologickom vyšetrení zistila invázia TCC, z toho: u jedného intravaskulárna, u 6 endolymfatická, u jedného intravaskulárna a endolymfatická a u 3 intravaskulárna, endolymfatická a perineurálna. Vyšetrenie separovanej krvi pred a po operácii farbením HE a PAP a na CK-7, CK-20 bolo takmer vo všetkých vzorkách negatívne. Pri IH tkaniva TCC na CK-7, CK-20, stromelysin bola pozitivita v 97,7 %, 74,4 % a 97,7 %. Cytologické vyšetrenie moču bolo pozitívne u 19 (50 %) z pacientov a korelovalo s vyšším grade G3 u 20 (46,5 %) pacientov. Expresia Ki-67 bola u pacientov s G3 (31,15 %) signifikantne vyššia ako u pacientov s G1 (7,53 %) (p < 0,01). Pri skúmaní TCC tkaniva sa nenašiel signifikantný vzťah medzi grade a expresiou p53 a stromelysinu. Záver: Testy neukázali zmeny expresie génov pre EGFR a UP-II v periférnej krvi a v imuno-separovaných bunkách pacientov pred a po operačnom zákroku. Výsledky v tomto súbore pacientov s TCC s prevažne nižším štádiom pTNM nepotvrdili výskyt CNB TCC v periférnej krvi.

Backgrounds: The aim of this pilot study was to investigate whether UP-II and EGFR genes expression detection with RT-PCR and the use of immunohistochemistry methods on patient samples taken before and after surgery could be used as a cancer marker for detection of circulating tumor cells in peripheral blood of patients with TCC. Another goal of this study was to identify whether surgery can influence the amount of circulating tumor cells and to correlate the samples with standard histopathological staging. Materials and Methods: A total of 43 patients with histologically proven TTC was enrolled in the study. There were 33 men and 10 women in the sample, mean age was 65 ± 12 years (range 37–85 years). Forty (93.0%) patients had TCC of the urinary bladder, 2 (4.6%) had TCC of renal pelvis and 1 (2.3%) had TCC of urinary bladder, urethra, and renal pelvis. A sample of 10 ml of peripheral blood was collected from each patient before and within 1 hour after a surgery. Blood samples were used for immunomagnetic separation of circulating tumor cells and determination of UP-II and EGFR genes expression. Subsequently, cancer tissue was processed, endolymphatic, intravascular and peritoneal invasion determined and CK-7, CK-20, stromelysin, Ki-67 and p53 expression evaluated. Blood samples taken before and after the surgery were also subjected to immunohistochemical analysis using hematoxylin-eosin (HE) staining and staining by Papanicolaus (PAP). CK-7 and CK-20 expression was also evaluated. Results: EGFR and UP-II were expressed in 24 of the 35 (68.6%) and in 19 of the 35 (54.3%) cancer tissues samples, respectively. EGFR was expressed neither in blood samples nor in immuno-separated cell samples. UP-II was expressed in 1 of the 19 (5.3%) samples of immuno-separated cells acquired before the surgery and in no sample of immuno-separated cells obtained after the surgery (P < 0.9999). Moreover, UP-II was expressed in 2 of the 32 (6.3%) whole blood samples taken before the surgery and in 3 out of 32 (9.4%) whole blood samples taken within an hour after the surgery (P < 0.9999). Histopathological examination showed TCC invasion in 11 of the 43 patients: 1 patient with intravascular, 6 with endolymphatic, 1 with intravascular and endolymphatic and 3 with intravascular, endolymphatic and perineural invasion. Immunohistochemical examination of separated blood before and after the surgery by PAP and HE staining, CK-7 and CK-20 expression were negative in nearly all samples. Immunohistochemical examination of TCC tissue showed positive results in 97.7% for CK-7expression, 74.4% for CK-20 and 97.7% for stromelysin. Cytological examination of urine was positive in 19 (50%) patients and correlated well with higher grade G3 in 20 (46.5%) patients. Ki-67 expression was significantly higher in patients with G3 (31.15%) in comparison to patients with G1 (7.53%) (p < 0.01). There was no significant association between grade and expression of p53 and stromelysin in cancer tissue. Conclusion: Our preliminary tests did not show any significant change to EGFR and UP-II expression in peripheral blood and in immuno-separated cells before and after a surgery. The results for a group of patients with lower pTNM grade did not confirm the presence of malignant urothelial cells in peripheral blood.

• MeSH
• dospělí MeSH
• erbB receptory genetika   krev   MeSH
• exprese genu MeSH
• karcinom z přechodných buněk diagnóza   genetika   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   krev   MeSH
• nádorové biomarkery krev   MeSH
• nádorové cirkulující buňky MeSH
• pilotní projekty MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• urologické nádory diagnóza   genetika   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH

• Publikační typ
• abstrakty MeSH

Úvod/cieľ: Asociácia génov CDKAL1 a KCNQ1 s diabetes mellitus 2. typu (DM2T) bola potvrdená viacerými celogénomovými asociačnými štúdiami v kaukazskej aj ázijskej populácii. U oboch génov sa predpokladá vplyv na riziko rozvoja DM2T prostredníctvom poruchy inzulínovej sekrécie. Vychádzali sme z predpokladu, že prítomnosť rizikovej alely môže predisponovať k skoršiemu nástupu DM2T. Cieľom našej štúdie bolo zistiť frekvenciu rizikových alel polymorfizmov rs7756992 génu CDKAL1 a rs163184 génu KCNQ1 a analyzovať ich vzťah k veku stanovenia diagnózy DM2T v populácii Slovenska. Metódy: V súbore 538 pacientov s DM2T boli určené genotypy polymorfizmu rs7756992 A/G génu CDKAL1 a polymorfizmu rs163184 G/T génu KCNQ1 metódou asymetrickej PCR s následnou analýzou krivky topenia. Antropometrické a laboratórne parametre boli vyšetrené štandardnými metódami. Vzhľadom na analýzu 2 génov bola definovaná požadovaná hladina štatistickej významnosti na hladine p < 0,025. Výsledky: Rizikoví homozygoti (GG) polymorfizmu KCNQ1 mali v recesívnom modeli o 2 roky vyšší priemerný vek diagnózy DM2T ako nosiči alely T (GT + TT), ale hodnota štatistickej významnosti nedosiahla preddefinovanú úroveň. Pri polymorfizme génu CDKAL1 nebol pozorovaný signifikantný rozdiel vo veku diagnózy DM2T medzi jednotlivými genotypmi. Záver: V tejto štúdii sme nezistili vzťah medzi sledovanými polymorfizmami génov CDKAL1 a KCNQ1 a skorším vekom nástupu DM2T v populácii Slovenska.

Background/aims: The association of CDKAL1 and KCNQ1 genes with type 2 diabetes mellitus (DM2T) was confirmed by several genome-wide association studies in both Caucasian and Asian populations. For both genes, it is supposed that the risk of DM2T development is related to impaired insulin secretion. Based on assumption that the presence of risk allele might predispose to an earlier onset of DM2T, the aim of the present study was to assess the frequency of risk alleles of CDKAL1 rs7756992 and KCNQ1 rs163184 poly­morphisms and to analyze their association with the age at DM2T diagnosis in the Slovakian population. Methods: CDKAL1 rs7756992 A/G and KCNQ1 rs163184 G/T polymorphisms were genotyped using asymmetric PCR with subsequent melting curve analysis in a group of 538 patients with DM2T. Anthropometric and laboratory parameters were determined by using standard methods. Since two genes were analysed, the required level for statistical significance was defined as p < 0.025. Results: Risk homozygotes (GG) for KCNQ1 polymorphism had higher mean age of DM2T diagnosis by 2 years when compared to T-allele carriers (GT + TT) in a recessive model, but the difference did not reach the predefined level of statistical significance. No relationship of CDKAL1 polymorphism to the age at onset of DM2T diagnosis was observed. Conclusions: In the present study, no relationship of CDKAL1 and KCNQ1 polymorphisms to the earlier onset of type 2 diabetes was observed.

• MeSH
• celogenomová asociační studie MeSH
• cyklin-dependentní kinasa 5 genetika   MeSH
• diabetes mellitus 2. typu diagnóza   genetika   MeSH
• draslíkový kanál KCNQ1 genetika   MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• senioři MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Slovenská republika MeSH

Úvod/Cieľ: Asociácia polymorfizmu génu transkripčného faktora TCF7L2 rs7903146 C/T s výskytom diabetu mellitu 2. typu (DM2) predstavuje doteraz najsilnejšiu opísanú asociáciu (zvýšenie rizika DM2 o 40 %). Asociácia pre tento polymorfizmus bola replikovaná vo viacerých svetových populáciách, avšak sila asociácie, ako aj frekvencia rizikovej alely T je rozdielna medzi populáciami. Cieľom štúdie bolo replikovať asociáciu TCF7L2 rs7903146 C/T s DM2 v populácii Slovenska a určiť frekvenciu rizikovej alely T. Metódy: U 538 pacientov s DM2 a 361 účastníkov s normálnou glukózovou toleranciou (kontroly) sme určili genotypy polymorfizmu TCF7L2 rs7903146 C/T metódou asymetrickej PCR s neznačenými oligonukleotidmi s analýzou meltingovej krivky. Antropometrické a laboratórne parametre boli vyšetrené štandardnými metódami. Výsledky: Frekvencia zriedkavejšej, rizikovej alely T bola vyššia v skupine DM2 v porovnaní s kontrolnou skupinou (30 % vz. 28 %), čo predstavovalo v log-aditívnom modeli signifikantné zvýšenie rizika per allelam skoro o 30 % (OR 1,29; 95 % KI 1,00 - 1,66; p = 0,048). Zastúpenie genotypu T/T bolo signifikantne vyššie v skupine pacientov s DM2 (11 %) v porovnaní s kontrolami (6 %) (59/538 vz. 21/361; p = 0,015) a po korekcii na vek, pohlavie a BMI bol genotyp T/T asociovaný s vyšším rizikom DM2 (OR 2,57; 95 % KI 1,40 - 4,73; p = 0,002) v porovnaní s nosičmi alely C (C/T + C/C). Záver: Replikovali sme asociáciu polymorfizmu TCF7L2 rs7903146 C/T s vyšším rizikom diabetu mellitu 2. typu v populácii Slovenska. Frekvencia rizikovej alely T a sila asociácie s DM2 sú v populácii Slovenska porovnateľné s inými kaukazoidnými populáciami.

Background/Aim: Polymorphism of the transcription factor gene TCF7L2 rs7903146 C/T has shown so far the strongest and best replicated association with type 2 diabetes (DM2), T-allele carrying 40 % increased risk. Although widely replicated, rs7903146 has shown marked variation in both frequency of the minor T-allele as well as the strength of association with DM2 among populations. Aim of this study was to replicate the association between TCF7L2 rs7903146 C/T and DM2 in the Slovakian population and to estimate frequency of the risk allele T. Methods: 538 DM2 patients and 361 subjects with normal glucose tolerance were genotyped for TCF7L2 rs7903146 C/T by assymetric PCR with unlabeled dyes and melting curve analysis. Anthropometric and biochemical examinations were performed by routine methods. Results: Minor, risk allele frequency (T) was higher among DM2 patients compared with controls (30 % vs. 28 %), which resulted in significant 30 % increased risk per T allele in the log-additive genetic model (OR 1,29; 95 % CI 1,00 - 1,66; p = 0,048). Genotype T/T was more prevalent among DM2 (11 %) than in controls (6 %) (59/538 vs. 21/361; p = 0,015). Adjusted for age, sex and BMI, genotype T/T was associated with increased risk of DM2 (OR 2,57; 95 %CI 1,40 - 4,73; p = 0,002) compared with C-allele carriers (C/T + C/C). Conclusion: We replicated association of TCF7L2 rs7903146 C/T with increased risk of type 2 diabetes in the Slovakian population. Both minor (risk) allele frequency (T) and the strength of association with DM2 is comparable with the other Caucasian populations.