Factors associated with all-cause mortality following endovascular abdominal aortic aneurysm repair.

Background: Knowledge of factors that influence all-cause mortality after endovascular abdominal aortic aneurysm repair (EVAR) could improve therapeutic strategies post-EVAR and thus patient prognosis. Our study aimed to evaluate the association between sociodemographic information, comorbidities, laboratory parameters, treatment, selected anatomical and genetic factors and all-cause mortality post-EVAR. Patients and methods: We reviewed all patients who had undergone elective EVAR for non-ruptured abdominal aortic aneurysm (AAA) between January 2010 and December 2019. AAA size (maximum diameter and volume) was measured using CT-angiography. Sac expansion was defined as at least 5 mm increase, sac regression as at least 5 mm decrease in the sac diameter determined at 36±3 months post-EVAR in relation to pre-EVAR AAA diameter. Adjustments were performed for age, hypertension, diabetes mellitus, dyslipidaemia, sex, smoking, number of lumbar arteries, patency of inferior mesenteric artery and number of reinterventions post-EVAR. Results: One hundred and sixty-two patients (150 men, 12 women) with a mean age of 72.6±7.3 years were included in the analysis. Pre-EVAR AAA diameter (HR 1.07; 95% CI 1.03 - 1.12; p=0.001), pre-EVAR AAA volume (HR 1.01; 95% CI 1.002 - 1.011; p=0.008), post-EVAR sac diameter (HR 1.06; 95% CI 1.03 - 1.10; p=0.000), post-EVAR sac volume (HR 1.01; 95% CI 1.002 - 1.011; p=0.006) and anticoagulation therapy (HR 2.46; 95% CI 1.18 - 5.14; p=0.019) were associated with higher mortality in multivariate analysis. Sac regression (HR 0.42; 95% CI 0.22 - 0.82; p=0.011), and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (HR 0.71; 95% CI 0.36 - 0.97; p=0.047) were associated with lower mortality. Conclusions: Greater pre- and post-EVAR diameter and volume, failure of sac regression and anticoagulation were associated with higher mortality post-EVAR. Reduced mortality was observed in patients treated with ACE inhibitors or ARBs, and in patients with AAA sac regression.

Evaluation of 5-HTTLPR (insertion/deletion) and BDNF (rs6265) genetic variations in the Slovakian individuals suffering from affective disorders.

The pathophysiology of affective disorders (AD), including depressive disorders (DD) and anxiety disorders (ANXD), is still unclear. To understand risk factors of the disorders, we evaluated genetic variations of the serotonin reuptake transporter (5-HTTLPR, ins/del) and the brain-derived neurotrophic factor (BDNF, rs6265) in Slovak patients suffering from AD. After genotyping we observed a significantly increased frequency of LS and LL genotypes (5-HTTLPR) in individuals diagnosed with AD compared to controls (OR = 1.99, 95% CI = 1.21-3.27, p = 0.006). There was also a significant relationship between TT (BDNF) genotype and the risk of AD in males (OR = 5.93, 95% CI = 1.42-27.07, p = 0.011). In gene-gene analysis, the LL or LS (5-HTTLPR) and CT or TT (BDNF) genotype combinations had a risk-enhancing effect on AD susceptibility (mainly ANXD in males), while SS (5-HTTLPR) and TT (BDNF) combination had a protective effect on AD risk (mainly ANXD). However, larger prospective studies are needed to confirm our findings.

Higher preprocedural fibrinogen levels are associated with aneurysm sac regression after EVAR.

Background: The aim of our study was to determine the diameter of the aneurysm sac 24 months after endovascular abdominal aortic aneurysm repair (EVAR); to identify factors associated with sac regression, and to determine the impact of sac regression on all-cause mortality during long-term follow-up. Patients and methods: We conducted a retrospective review of prospectively collected data from patients treated with EVAR between January, 2010 and July, 2016. Sac regression was defined as at least 5 mm decrease in aneurysm diameter in relation to the preprocedural diameter seen on computed tomography angiography. Sociodemographic information, comorbidities, treatment, laboratory parameters, selected anatomical and genetic factors were all analysed to determine their impact on sac regression. Results: During the study period, 124 patients with mean age of 71.2 ± 7.2 years met the inclusion criteria. Sac regression was found in 45.2% of patients. Higher preprocedural fibrinogen was found in patients with sac regression in comparison with patients with stable sac or sac expansion (3.84 g/l vs 3.47 g/l; p = 0.028). In multivariate analysis after adjustment for age, hypertension, sex, smoking, dyslipidaemia, volume and percentage of intraluminal thrombus higher fibrinogen was associated with an increased probability of sac regression (OR 2.47; 95% CI 1.29-4.72; p = 0.006). Persistent type II endoleak was associated with significantly lower probability of sac regression in univariate and multivariate analysis after adjustment for age, hypertension, sex, smoking and dyslipidaemia (OR 0.26; 95% CI 0.10-0.66; p = 0.004). Higher age was a significant predictor of sac regression in multivariate analysis after adjustment for hypertension, sex, smoking and dyslipidaemia (OR 1.07; 95% CI 1.02-1.14; p = 0.012). No difference was found between patient subgroups with and without sac regression in all-cause mortality during follow-up. Conclusions: Higher preprocedural fibrinogen, absence of persistent type II endoleak and higher age were predictive factors of aneurysm sac regression post-EVAR.

Association of JAG1 gene polymorphism with systemic blood pressure in patients with obstructive sleep apnea: a prospective cohort study.

AIM: To assess the effects of single nucleotide polymorphisms (SNPs) on blood pressure control in patients with obstructive sleep apnea (OSA). METHODS: This prospective observational cohort study, conducted between 2004 and 2014, examined the associations of SNPs of JAG1, GUCY1A3-GUCY1B3, SH2B3, and NPR3-C5orf23 genes with systolic and diastolic blood pressure (SBP, DBP) in 1179 adults evaluated for OSA with overnight polysomnography. Genotyping was performed by unlabeled probe melting analysis. RESULTS: The patients were predominantly male (69.6%, mean age 52±11 years, apnea-hypopnea index 34±31 episodes/h). Only JAG1 genotype was associated with SBP and DBP: compared with AA homozygotes, G allele carriers (pooled GG and AG genotype) had significantly higher morning SBP (132±19 vs 129±18 mm Hg; P=0.009) and morning and evening DBP (85±11 vs 83±10 mm Hg, P=0.004; 86±10 vs 84±10 mm Hg, P=0.012, respectively); the differences remained significant after the correction for multiple SNPs testing. In multivariate analyses, oxygen desaturation index and JAG1 genotype independently predicted morning SBP (P=0.001, P=0.003, respectively) and DBP (P<0.001, P=0.005, respectively), and evening SBP (P=0.019, P=0.048, respectively) and DBP (P=0.018, P=0.018, respectively). CONCLUSION: This is the first replication study of the SNPs recently linked to arterial hypertension in general population by genome-wide association studies. Our findings suggest that JAG1 genotype is related to blood pressure control in OSA: G allele was associated with higher morning and evening SBP and DBP.

Risk allele of gene variant rs6584389 is associated with increased intima-media thickness in patients with type 2 diabetes.

BACKGROUND: Genome-wide association studies identified several gene variants associated with peripheral arterial disease (PAD). Among them, rs6584389 A>C was significantly associated with PAD defined by decreased ankle-brachial index (ABI). The aim of this study was to investigate whether the rs6584389 variant is also associated with the earlier stages of atherosclerosis assessed by intima-media thickness (IMT) or pulse-wave velocity (PWV) in clinically asymptomatic subjects with type 2 diabetes (T2DM), a group of patients with a high cardiovascular risk. PATIENTS AND METHODS: In total, 111 patients with T2DM (56 females, 55 males) with a mean age 63.0 ± 9.1 years were consecutively included in the study. IMT was measured by ultrasound using 7 MHz linear transducer. PWV was measured using a piezoelectric method. Genotyping for rs6584389 was performed by PCR-HRMA method. RESULTS: The carriers of the risk C-allele of rs6584389 variant had significantly higher mean left-side IMT (AA: 0.67 ± 0.12, AC 0.77 ± 0.21, CC 0.78 ± 0.22 mm; p = 0.04). In multiple linear regression analysis, rs6586389 genotype was significantly associated with all measured IMT parameters. The presence of each risk C-allele predicted an increase in left-side IMT by 0.056 mm (p = 0.017), right-side IMT by 0.053 mm (p = 0.039), average IMT by 0.054 mm (p = 0.023), and maximal IMT by 0.058 mm (p = 0.021). Age and HbA1c levels were also significantly associated with increased IMT in all multivariate models. CONCLUSIONS: Gene variant rs6584389 A>C near to PAX2 gene was associated with increased carotid IMT in patients with type 2 diabetes independently of the other main risk factors for atherosclerosis.

Gene Polymorphism of the Adenosine A2a Receptor in Patients with Vasovagal Syncope.

BACKGROUND: Adenosine may play a role in the pathogenesis of vasovagal syncope (VVS). The aim of the study was to evaluate the adenosine A(2A) receptor gene 1083 T > C polymorphism in patients with syncope and its possible association with results of head-up tilt test (HUT). METHODS: Three hundred and forty-seven consecutive patients (mean age 47.3 ± 18.5 years, 132 men, 215 women) with one or more syncopal episodes underwent HUT as part of standardized diagnostic evaluation. HUT was positive in 207 patients (75 males, mean age 44.7 ± 18.6 years) and negative in 140 patients (58 males, mean age 48.17 ± 18.8 years). One thousand and eighty-three T > C single nucleotide polymorphism in the adenosine A(2A) receptor gene (rs5751876) was evaluated in 347 patients with syncope and in 85 subjects without history of syncope (54 men, mean age 41.7 ± 16.3). RESULTS: Adenosine A(2A) receptor 1083 T > C polymorphism was not associated with the positivity of HUT. Blood pressure and heart rate response to tilting was similar in all genotypes. Low frequency (LF) power was significantly lower in CC genotype compared to CT genotype in early phase of tilt (log LF 2.69 ± 0.61 vs 3.20 ± 0.60; P = 0.01) and at the time of syncope (log LF 2.60 ± 0.63 vs 2.77 ± 0.48; P = 0.04). CONCLUSIONS: Adenosine A(2A) receptor 1083 T > C polymorphism is not associated with the positivity of HUT and its proposed role in predisposition to VVS was not confirmed. CC genotype may be associated with lower sympathetic activity during HUT.

A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes.

PURPOSE: The aim of the present study was to investigate possible associations of the single-nucleotide variants in six genes encoding the key molecules mediating the metformin pharmacodynamic effect with the response to treatment with metformin in patients with type 2 diabetes. METHODS: One hundred forty-eight drug-naïve patients with type 2 diabetes were included in the study. PRKAA1 rs249429, STK11 rs741765, PCK1 rs4810083, PPARGC1A rs10213440, HNF1A rs11086926, and CAPN10 rs3792269 variants were genotyped. The outcomes of the study were treatment success defined by achieving HbA1c <7 % and absolute reduction in HbAlc after 6-month metformin therapy. The relationships between genotypes and outcomes were evaluated in multivariate logistic and linear models. The level of statistical significance after Bonferroni correction was predefined as p<0.0083. RESULTS: The minor G-allele of CAPN10 rs3792269 A>G polymorphism was significantly associated with less treatment success with an odds ratio of 0.27 (95 % CI 0.12-0.62, p=0.002) per variant allele. When the reduction in HbA1c was analyzed as a quantitative trait, G-allele was nominally associated with a smaller reduction in HbA1c (per allele ß=-0.26, 95 % CI -0.50 to -0.02, p=0.032). The reduction in HbA1c in minor allele carriers (24 % of study population) was smaller by 0.3 % in comparison with the major allele homozygotes. CONCLUSIONS: The present study provides the first observation of an association between a variant in CAPN10 gene and the response to metformin therapy in patients with type 2 diabetes. This observation needs to be replicated in further studies in different populations.

MDR1 polymorphisms and idiopathic nephrotic syndrome in Slovak children: preliminary results.

BACKGROUND: The role of the multidrug resistance-1 (MDR1 or ABCB1) gene polymorphisms 1236T>C, 2677T>G, and 3435T>C was studied in relation to susceptibility, demographics, and pathological characteristics, as well as their role in the therapeutic response (TR) to prednisone treatment in children with idiopathic nephrotic syndrome (INS). MATERIAL/METHODS: The polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method in 46 children with INS and in 100 healthy controls. Different genetic models (codominant, dominant, recessive, and overdominant) were used for testing of associations between polymorphisms and phenotypes. RESULTS: Statistical analysis showed a significantly increased chance of TR in children carrying 3435TC genotype (OR=5.13, 95% CI=1.18-22.25; overdominant model). Moreover, INS patients under 6 years of age had significantly decreased frequencies of MDR1 1236CC (7.7% vs. 35%, p=0.029) or 2677GG (3.8% vs. 30.0%, p=0.033) genotypes. We also observed that patients with minimal change in disease and patients under 6 years of age at the onset of INS were initial responders more frequently when compared with children with focal segmental glomerulosclerosis and patients ≥6 years old at the onset (p=0.0001, p=0.027, respectively). CONCLUSIONS: These data suggest that prednisone TR may be influenced by histology, age at the onset of INS, and MDR1 3435T>C polymorphism. The MDR1 1236T>C and 2677T>G polymorphisms were significantly associated with age at onset. Larger multicenter studies and studies across other ethnic groups are needed to elucidate the contradictory implications of MDR1 polymorphisms with INS in children.

Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea.

There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA. 519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR. In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in ε2 carriers and the ε3/ε3 genotype only. Nevertheless, the ε4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk ε4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic ε4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p=0.009 and p<0.001, respectively; R(2)=0.148) and ApoB levels (p=0.001 and p=0.003, respectively; R(2)=0.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA.

BDNF rs962369 Is Associated with Major Depressive Disorder.

This study enrolled 291 patients diagnosed with depression and schizophrenia (F32, F33, and F20 according to ICD-10) and 227 ethnicity-matched control subjects. We analyzed the distribution of BDNF rs6265 and BDNF rs962369 genotypes, finding no significant associations between these and schizophrenia. We revealed a significant increase in the risk of single-episode major depression disorder (MDD) for rs962369 minor allele homozygotes (CC vs. TT+TC), an association that persisted after adjusting for age and sex (OR 3.47; 95% CI 1.36-8.85; p = 0.009). Furthermore, rs962369 genotype was significantly associated with an increased risk of recurrent MDD in a log-additive model (OR per C-allele 1.65; 95% CI 1.11-2.45; p = 0.013). A comparative analysis between MDD subtypes and between MDD subtypes and schizophrenia showed no significant differences for BDNF rs6265. Notably, the frequency of minor allele C of BDNF rs962369 varied across subgroups, with the highest frequency in patients with recurrent MDD (0.32) and the lowest in schizophrenia patients (0.20). The presence of genotypes with at least one minor allele C was significantly higher in the recurrent MDD patient group compared to the schizophrenia group. In conclusion, the BDNF rs962369 variant was associated with MDD but not with schizophrenia.

Association Study of BDNF, SLC6A4, and FTO Genetic Variants with Schizophrenia Spectrum Disorders.

Schizophrenia spectrum disorders (patients with a diagnosis of schizophrenia, schizotypal, and delusional disorders: F20-F29 according to International Classification of Diseases 10th revision (ICD-10)) are considered highly heritable heterogeneous psychiatric conditions. Their pathophysiology is multifactorial with involved dysregulated serotonergic neurotransmission and synaptic plasticity. The present study aimed to evaluate the association of SLC6A4 (5-HTTLPR), FTO (rs9939609), and BDNF (rs6265, rs962369) polymorphisms with schizophrenia spectrum disorders in Slovak patients. We analyzed the genotypes of 150 patients with schizophrenia, schizotypal, and delusional disorders and compared them with genotypes from 178 healthy volunteers. We have found a marginally protective effect of LS + SS genotypes of 5-HTTLPR variant of the serotonin transporter SLC6A4 gene against the development of schizophrenia spectrum disorders, but the result failed to remain significant after Bonferroni correction. Similarly, we have not proven any significant association between other selected genetic variants and schizophrenia and related disorders. Studies including a higher number of subjects are warranted to reliably confirm the presence or absence of the studied associations.

Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia.

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 (5-HTTLPR), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.

Closed tube method for rapid screening of IL28B polymorphisms involved in response to hepatitis C treatment.

BACKGROUND & AIM: Hepatitis C is a liver disease caused by the hepatitis C virus. Interferon and ribavirin combination therapy has been a standard treatment of chronic hepatitis C. But only about 50% of patients have positive response to treatment and achieve so called sustained virological response. Recent studies indicate association of several single nucleotide polymorphisms near IL28B gene and response of hepatitis C patients to combined interferon/ribavirin treatment. In this study, rapid, specific and cost-effective small amplicon genotyping method for the two clinically important polymorphisms, rs12979860 C > T and rs8099917 T > G, near the IL28B gene is described. METHODS: The distribution of genotypes of 181 HCV-uninfected Slovak Caucasians was analyzed using this novel method, based on a real-time melting analysis of the small amplicon. RESULTS AND CONCLUSIONS: The frequency of wild-type (TT) homozygotes for rs8099917 was 66.30%, frequency of heterozygotes (TG) was 30.94% and we found only 2.76% subjects homozygous for risk G allele (allelic frequencies: T = 81.77%, G = 18.23%) were found. The frequency of wild-type genotype (CC) for rs12979860 was 49.72%, frequencies of heterozygous (CT) and risk-allele homozygous genotypes (TT) were 39.78% and 10.50%, respectively (allele frequencies: C = 69.61%, T = 30.39%). Statistically significant differences in the distribution of the alleles between the men and the women were not found. The novel method developed in our laboratory proved to be simple and highly customizable.

Positive association between calcium channel blocker treatment and persistent type II endoleak.

BACKGROUND: Type II endoleaks are the most common complication occurring after endovascular abdominal aortic aneurysm repair (EVAR). The aims of our study were to evaluate the impact of persistent type II endoleak on sac dynamics post-EVAR, and to study the association between non-anatomical factors including polymorphisms associated with abdominal aortic aneurysm (AAA) and persistent type II endoleak. METHODS: The cohort comprises 210 patients undergoing EVAR between January 2010 and December 2018. A persistent type II endoleak was defined as any type II endoleak lasting longer than six months and included also a type II endoleak diagnosed after six months or more post-EVAR during the 36-month follow-up period confirmed with CT-angiography. Anteroposterior AAA maximum diameter and AAA volume were measured pre-EVAR and 36 months post-EVAR using CT-angiographic pictures. Sac progression was defined as at least 5 mm increase, sac regression as at least 5 mm decrease in the sac diameter in relation to the preprocedural diameter. Sociodemographic information, comorbidities, treatment, laboratory parameters, selected anatomical and genetic factors were all analyzed to determine their impact on persistent type II endoleak. The adjustments included age, hypertension, diabetes mellitus, dyslipidemia, sex, smoking in multivariate analyses. When postprocedural diameter and volume were evaluated, adjustments included also preprocedural diameter/volume. RESULTS: After exclusion, 178 patients with mean age 72.4±7.60 years remained for analysis. Persistent type II endoleak was found in 27.5% of patients (N.=49) and 2.94-times increased risk of sac progression in multivariate analysis (P=0.033). In multivariate analysis, AAA diameter in patients with persistent type II endoleak was 4.31 mm greater than in patients without (B=4.31; P=0.014); and its presence was also associated with 22.0 cm3 greater sac volume (B=22.0; P=0.034) compared to patients without persistent type II endoleak. Treatment with calcium channel blockers increased risk of persistent type II endoleak 2.11-times in multivariate analysis (OR=2.11; 95% CI: 1.05-4.25; P=0.037). No association between persistent type II endoleak and selected polymorphisms associated with AAA and other observed factors were found. CONCLUSIONS: Risk of persistent type II endoleak was more than doubled in patients taking calcium channel blockers. Patients with persistent type II endoleak had greater anteroposterior sac diameter and sac volume compared to patients without persistent type II endoleak.

Effect of NAT2 gene polymorphism on bladder cancer risk in Slovak population.

N-acetyltransferase 2 (NAT2) is phase II enzyme with major roles in catalyzing the detoxification of aromatic amines, which are known risk factors for bladder cancer, and are ubiquitously present in the environment. We assessed the association between common polymorphisms in NAT2 gene and the risk of bladder cancer in 90 Slovak patients and 274 ethnicity-matched healthy controls. Effect modifications by smoking, age and gender were also evaluated. Overall, NAT2 slow acetylation was associated with significantly increased risk of bladder cancer (OR = 1.90; 95% CI, 1.15-3.16). In stratified analyses by age and gender, the elevated risk conferred by slow acetylator genotype was evident in older individuals (OR = 3.55; 95% CI, 1.77-7.35) and males (OR = 4.65; 95% CI, 1.68-16.10), with further increasing in NAT2*5B/*6A genotype carriers. Smoking was confirmed to be important risk factor, moreover, the risk was markedly increased in smokers with NAT2 slow acetylator genotype, and NAT2*5B/*6A carriers especially. In summary, these findings are consistent with previous literature suggesting that individual susceptibility to bladder cancer may be modulated by NAT2 polymorphisms, particularly in interaction with relevant environmental exposures such as smoking.

[Genetic polymorphisms as new predictive factors for successful treatment of chronic hepatitis C]. / Genetické polymorfizmy ako nové prediktívne faktory uspesnosti liecby chronickej hepatitídy C.

Currently, the gold standard for the treatment of chronic hepatitis C is combination therapy with pegylated interferon alpha and ribavirin. Despite advances in treatment modalities, only 50 % of patients achieve sustained virological response. Therefore, determination of predictive factors related to response to therapy is very important. In 2009, three independent studies concerning genome-wide association identified several single nucleotide polymorphisms near the IL-28 gene, associated with virological response. Hence, it appears that genetic polymorphism may become important predictive factors. All patients beginning therapy, will probably be tested for the presence of these polymorphisms, allowing individualized treatment options for every patient.

The prevalence of Gly972Arg and C825T polymorphisms in Slovak women with polycystic ovary syndrome and their relation to the metabolic syndrome.

AIM: To assess the prevalence of IRS-1 Gly972Arg and GNB3 C825T polymorphisms in women with polycystic ovary syndrome (PCOS) and their relation to the metabolic syndrome and hyperandrogenaemia. METHODS: Fifty-three female patients with diagnosis of PCOS and 21 healthy women were genotyped for the commom Gly972Arg and C825T polymorphisms. Body mass index, serum glucose, insulin, insulin sensitivity index HOMA (homeostasis model assessment) and serum lipoproteins were estimated. RESULTS: The prevalence of Gly972Arg genotype in PCOS women was 22.64% and was not significantly higher than in control group with the prevalence 9.52%. The frequency of T alleles was 28% in PCOS group that was similar to control group (29%). We did not find the significant differences in the frequency of TC + TT genotypes between patients and controls. There were no significant differences in serum glucose, insulin, lipoproteins, index HOMA, as well as BMI and waist circumference between patients with GlyArg and GlyGly. Both CC and TC/TT genotype patients had similar values of BMI, waist and measured biochemical variables. Moreover, Gly972Arg and C825T polymorphisms were not related to hormonal status of PCOS women. CONCLUSION: The Gly972Arg and C825T polymorphisms are associated neither with PCOS nor with metabolic syndrome in the Slovak female population.

Whole exome sequencing identifies a homozygous POLG2 missense variant in an adult patient presenting with optic atrophy, movement disorders, premature ovarian failure and mitochondrial DNA depletion.

POLG2 associated disorders belong to the group of mitochondrial DNA (mtDNA) diseases and present with a heterogeneous clinical spectrum, various age of onset, and disease severity. We report a 39-year old female presenting with childhood-onset and progressive neuroophthalmic manifestation with optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia and generalized chorea associated with mtDNA depletion. Whole-exome sequencing identified an ultra-rare homozygous missense mutation located at Chr17: 062474101-C > A (p.Asp433Tyr) in nuclear POLG2 gene encoding PolγB, an accessory subunits of mitochondrial polymerase γ responsible for mtDNA replication. The healthy parents and 2 sisters of the patient were heterozygous for the variant. To our best knowledge, this is the first case of homozygous variant in the POLG2 gene resulting in mitochondrial depletion syndrome in an adult patient and its clinical manifestations extend the clinical spectrum of POLG2 associated diseases.

The role of the -427T/C apolipoprotein E promoter polymorphism in the pathogenesis of Alzheimer's disease, vascular dementia and mixed dementia.

In this work, we explored the existence of genetic variant within the apolipoprotein E gene transcriptional regulatory region. Upon a population study, three polymorphic sites (-491, -427 and -219) and two mutations were found. We investigated newly reported -427T/C promoter polymorphism in association with sporadic Alzheimer's disease (AD), vascular (VD) and mixed dementia (MD) along with APOE genotype and gender. Observed polymorphisms were investigated in 267 subjects, 122 of them formed a control group, the group of patients consisted of 145 subjects. Sixty patients were diagnosed with AD, 41 patients were diagnosed with VD and 35 patients left were diagnosed with MD in Slovak Caucasians (Central Europe). Gene-gene interaction analysis showed increase of the risk to develop AD in subjects carrying both the at least one C allele and the APOE E4 allele (OR = 17.93, 95%CI = 3.50-171.54).

Beta2-adrenergic receptor haplotype and bronchodilator response to salbutamol in patients with acute exacerbations of COPD.

BACKGROUND: The role of the beta2-adrenergic receptor (ADRB2) genotype in patients with chronic obstructive pulmonary disease (COPD) is unclear. In patients with acute exacerbations of COPD (AECOPD), we assessed the role of ADRB2 haplotypes in morning lung function and in the bronchodilator response to salbutamol. MATERIAL/METHODS: In 107 patients with AECOPD, polymorphisms in the amino acid position 16 (Arg16/Gly16) and 27 (Gln27/Glu27) of the ADRB2 gene were assessed by allele-specific polymerase chain reaction, identifying 31 subjects with the Gly16/Glu27-negative and 76 with the Gly16/Glu27-positive ADRB2 haplotype. Pulmonary function and bronchodilator response to salbutamol were assessed using bodyplethysmography. RESULTS: Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were significantly higher in the Gly16/Glu27-negative compared to the Gly16/Glu27-positive haplotype group at baseline (49.7+/-2.9% vs 42.4+/-1.8% predicted, P=0.037; 44.0+/-2.2% vs 36.4+/-1.6% predicted, P=0.008, respectively). FEV1, PEF, and forced vital capacity (FVC) increased from baseline to after salbutamol treatment in both the Gly16/Glu27-negative and the Gly16/Glu27-positive ADRB2 haplotype groups (P<0.001 for all comparisons). Values for FEV1 and PEF after administration of the bronchodilator were significantly higher in the Gly16/Glu27-negative haplotype group compared with the Gly16/Glu27-positive haplotype group (P=0.030 and P=0.034, respectively). No differences were observed in DeltaFEV1, DeltaPEF, or DeltaFVC after bronchodilation between the 2 ADRB2 haplotype groups (12.2+/-1.8% vs 14.5+/-1.5% predicted, P=0.393; 12.2+/-3.3% vs 20.8+/-3.2% predicted, P=0.117; 9.1+/-2.3% vs 10.4+/-1.9% predicted, P=0.707, respectively). CONCLUSIONS: The present findings suggest that the ADBR2 gene haplotypes may affect the severity of obstructive ventilatory impairment but not the immediate response to salbutamol during AECOPD.