Single Nucleotid Polymorphisms Research Articles

Left common trunkus pulmonary veins have genetic background and poor rhythm outcome after atrial fibrillation catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background There is a genetic background in pulmonary vein (PV) development and atrial fibrillation (AF). However, the genetic trait of PV variations and their rhythm outcome after AF catheter ablation (AFCA) is unclear. Objective We explored the genetic and clinical characteristics and long-term rhythm outcomes of AF patients with PV variation or left common trunkus (LCT)-PV. Methods We included 2,897 AF patients (74.0% male, age 59.0 ± 10.7 years, 66.3% paroxysmal AF) with available genome-wide association study results, cardiac computed tomogram data, and protocol-based regular rhythm follow-up from the Yonsei AF ablation cohort database. We defined LCT-PV when the upper and lower PV separate at >10 mm distal to the left PV antrum margin. PV variations included both LCT-PV and accessory PVs. We analyzed the polygenic risk score (PRS) of 12 AF-associated genes (DSP, GJA1, HCN4, KCNQ1, NPPA, PITX2, RYR2, SCN5a, SHOX2, ATP2A2, TBX3, and TBX5) and long-term rhythm outcomes after AFCA. Results We found PV variation in 296 (10.2%) and LCT-PV in 102 (3.5%). PRS of 1,227 single nucleotid polymorphisms (SNPs) was significantly higher in PV variation patients (p=4.93e-08) and LCT-PV patients (p=1.95e-20). The patients with LCT-PV had higher CHA2DS2VASc scores (p=0.024) and lower atrial epicardial adipose tissue volume (p=0.034). During 39.7 ± 34.8 months follow-up period, LCT-PV patients had a significantly higher recurrence rate than their counter part in the paroxysmal AF sub-group (Log-rank p=0.036), but not in overall PV variations. LCT-PV with the highest 10% PRS was independently associated with AF recurrence after AFCA (HR 2.10, 95% CI 1.21-3.63, p=0.008). Conclusions Among the patients who underwent AFCA, PV variation, including LCT-PV, has a significant genetic background. The post-AFCA recurrence rate was significantly higher in patients with LCT-PV and high PRS, especially in paroxysmal AF.

Impact of FCGR2A R131H, FCGR3A F158V and FCGR3B NA1/NA2 polymorphisms on response to fc-containing TNF inhibitors in Tunisian rheumatoid arthritis patients.

Single nucleotid polymorphisms (SNPs) of Fc-gamma receptors (FcgRs), by inducing a variation of their affinity to the Fc-region of immunoglobulins, might influence the efficacy of Fc-containing biologics prescribed in rheumatoid arthritis (RA). Our aim was to investigate associations of FCGR2A, FCGR3A and FCGR3B SNPs with TNF-inhibitors (TNFi)' response in Tunisian RA patients. A cross-sectional, observational and analytic multicentric cohort study was conducted in a group of 47 Tunisian RA patients treated with (etanercept [ETA], adalimumab [ADL] and infliximab [IFX]). Treatment outcome was evaluated after 6months. R131H-FCGR2A, F158V-FCGR3A and NA1/NA2-FCGR3B SNPs were genotyped. The analytic study including all types of TNFi showed that FCGR3A-F/F low-affinity receptor was associated with a greater decrease of DAS28, while FCGR3B-NA1/NA1 high-affinity receptor was associated with a lower decrease of DAS28 in ADL group. Furthermore, both of high affinity receptors FCGR3B-NA1/NA1 and FCGR3A-V/V were more prevalent in non-responders to ADL, according to EULAR criteria. Identifying reliable biomarkers of response to biologics in RA is necessary to improve responsiveness, preserve joints' functions and structure, and reduce treatment's cost. Our study showed that FCGR3A and FCGR3B polymorphisms might have an impact on TNFis' response in RA Tunisian patients since bad response was more frequent in homozygous carriers of high affinity alleles FCGR3A-V and FCGR3B-NA1.

Club-mosses (Diphasiastrum, Lycopodiaceae) from the Far East – Introgression and possible cryptic speciation

Hybridization occurs often in the genus Diphasiastrum (Lycopodiaceae), which corroborates reports for the two other recognized lycophyte families, Isoëtaceae and Selaginellaceae. Here we investigate the case of D. alpinum and D. sitchense from the Russian Far East (Kamchatka). Their hybrid, D. × takedae, was morphologically recognizable in 16 out of 22 accessions showing molecular signatures of hybridization; the remaining accessions displayed the morphology of either D. alpinum (3) or D. sitchense (3). We sequenced markers for chloroplast microsatellites (cp, 175 accessions from Kamchatka) and for the two nuclear markers RPB and LFY (175 and 152 accessions). A selection of 42 accessions, including all hybrid accessions, was analysed via genotyping by sequencing (GBS). We found multiple, but apparently uniparental hybridization, clearly characterized by a deviating group of haplotypes for D. sitchense and all hybrids. All accessions showing molecular signatures of hybridization in nuclear markers revealed the parental haplotype of D. sitchense, however only the LFY marker differentiated between the parent species. GBS, including 69,819 quality-filtered single nucleotid polymorphisms, unambiguously identified the hybrids and revealed introgression to occur. Most of the hybrids were F1, but three turned out to be backcrosses with D. alpinum (one) and with D. sitchense (two). These observations are in contrast to prior findings on three European species and their intermediates where all three hybrids turned out to be independent F1 crosses without evidence of recent backcrossing. In this study, backcrossing was detected, which indicates a limited fertility of the hybrid taxon D. × takedae. A comparison of accessions of Kamchatkian D. alpinum with plants from Europe indicated possible cryptic speciation. Accessions from the Far East had (i) a lower DNA content (7.0 vs. 7.5 pg/2C), (ii) different prevailing cp haplotypes, and (iii) RPB genotypes, and (iv) a clearly different SNP pattern in GBS. Diphasiastrum sitchense and the similar D. nikoënse, for the latter additional accessions from Japan were investigated, appeared as forms of one diverse species, sharing genotypes in both nuclear markers, although chloroplast haplotypes and DNA content show slight variations.

Association of polymorphous light eruption with NOD-2 and TLR-5 gene polymorphisms.

Polymorphous light eruption (PLE) is a common, immunologically mediated, photosensitive skin disease. After ultraviolet-B (UV-B) irradiation, patients with PLE show reduced Langerhans cell (LC) depletion in the epidermis, which results in a non-suppressive microenvironment in the skin. Interestingly, severe acute graft-versus-host disease (aGvHD) occurred in stem cell transplanted patients that showed no or incomplete depletion of LCs after UVB irradiation. Genetic variation in nucleotide-binding oligomerization domain 2 (NOD-2) and toll-like receptor 5 (TLR-5) genes also confers susceptibility to aGvHD. We hypothesized that PLE is associated with genetic variation in the NOD-2 and TLR-5 genes. We investigated single-nucleotid polymorphisms (SNPs) of NOD-2 (R702W, G908R, 3020Cins) and TLR-5 (A592S, P616L, N392STOP) in skin biopsies of patients with PLE (n = 143) and in healthy controls (n = 104) using restriction fragment length polymorphism analysis. The frequency of NOD-2 alleles with the SNP R702W was significantly higher in PLE than in controls (31.8% vs. 6.3%; P < 0.0001), and homozygous carriers of this mutation were more common in PLE (27.9% vs. 0%; P < 0.0001). For SNP 3020Cins, the allele frequency (7.3% vs. 0.7%; P = 0.0025) and the number of heterozygotes (14.7% vs. 1.3%; P = 0.0019) were higher in PLE. The frequency of alleles with the N392STOP SNP of the TLR5 gene, which is associated with a truncated, non-functional receptor, was significantly higher in PLE (21% vs. 5%; 7% vs. 1% homozygotes, 28% vs. 8% heterozygotes; P < 0.0001). The other SNPs did not differ significantly. This study yielded a high frequency of functional SNPs in the NOD-2 and TLR-5 genes in PLE. The same SNPs are associated with aGvHD and there are similarities in the reaction of LCs after UVB irradiation between aGvHD and PLE. This leads to the hypothesis that patients with PLE may be more susceptible to developing GvHD after stem cell transplantation, an assumption that needs to be investigated further.

The interaction between genetic polymorphisms in FTO, MC4R and MTHFR genes and adherence to the Mediterranean Diet in relation to obesity.

To investigate the potential interaction between genetic background and adherence to the Mediterranean Diet, macronutrient intake and physical activity with regard to obesity in a sample of healthy adults. Cross-sectional epidemiological study including 392 adults living in the Mediterranean basin. Data including FFQ, IPAQ and sociodemographic questionnaires were collected via face-to-face interviews. Anthropometric measures were performed and saliva swab for DNA extraction. Two MD scores were calculated to assess the adherence of the population to this pattern. Three single nucleotid polymorphisms (SNPs) related to obesity were studied: FTO, MC4R, MTHFR. FTO rs9939609 is significantly associated with WHR, and MC4R with all phenotypic traits linked to obesity (BMI, WC and WHR). However, MTHFR polymorphism didn't show any significant correlation with anthropometric parameters. Adherence to the MD and high level of physical activity do not seem to protect against the occurrence of overweight and obesity in genetically predisposed subjects. Classic lifestyle interventions are insufficient in addressing the challenging obesity pandemic. Identifying more genetic variants and understanding their interaction with lifestyle will improve the clinical outcome of these variants for risk prediction and personalized nutrition and medical therapy. Also, the MD should undergo a redefinition adapted to each country on the Mediterranean basin in order to organize public health measures for its comeback.

Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study

BackgroundObesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network.MethodsWe analyzed 347 participants (age range: 20–59 years, BMI range: 17–38 kg/m2) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity.ResultsHigher BMI was significantly associated with lower connectivity strength for number of streamlines (β = −0.0025, 95%—C.I.: [−0.004, −0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (β = −0.0009, 95%—C.I. [−0.0016, −0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity.ConclusionsHere, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.

Triangular relationship between CYP2R1 gene polymorphism, serum 25(OH)D3 levels and T2DM in a Chinese rural population

BackgroundA low serum vitamin D concentration is associated with an increased risk of type 2 diabetes mellitus (T2DM). Recently, several single nucleotid polymorphisms (SNPs) have been identified which influence vitamin D levels. If a causal relationship exists between vitamin D concentrations and T2DM, one would expect a similar association between the newly identified SNPs and T2DM risk. Therefore, this study investigated the association between four SNPs of cytochrome P450 family 2, subfamily R, peptide 1 (CYP2R1) gene, serum 25(OH)D3 levels and T2DM. MethodsThree hundred and ninety-seven patients with confirmed T2DM, as well as 397 age- and gender-matched controls were enrolled in this case-control study. Genotyping was performed by TaqMan probe assays. Kruskal-Wallis one-way analysis and muitiple logistic regression analysis were performed to identify the possible risk genotype for vitamin D levels and T2DM, respectively. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-environment interactions. ResultsThe serum 25(OH)D3 levels were significant lower in the T2DM group. Significant differences were observed between patients and controls in terms of the genotype distributions of rs1993116 (P = 0.048) and rs10766197 (P = 0.024). Similarly, rs1993116 and rs10766197 polymorphisms were found to be significantly associated with T2DM risk. AG + GG genotype carriers of the rs1993116 and rs10766197 polymorphisms could have an increased risk of developing T2DM compared with AA carriers, the OR and 95% CI were 1.64 (1.09–2.46) and 1.76 (1.18–2.65), respectively. However, none of the tested SNPs were independently associated with serum 25(OH)D3 levels (P > 0.059). Gene-gene and gene-environment interaction analyses indicated that rs12794714-rs10766197 and rs12794714-vitamin D deficiency (VDD) models successfully predicted T2DM risk (P < 0.001). ConclusionsRs1993116 and rs10766197 polymorphisms of CYP2R1 gene may be novel genetic markers for T2DM in China. Given the lack of association between SNPs and serum 25(OH)D3 levels, well-designed future studies should be conducted with larger sample sizes in rural areas of China.

The Role of Molecular Karyotyping in the Genetic Etiology of Autism

The aim of this study was to investigate the deletions and duplications with a molecular karyotyping technique and to elucidate the etiology of autism. A total of 31 patients (20 boys and 11 girls) between 4 to 18 years old with normal chromosomal analysis and no Fragile X mutation were diagnosed in the Ege University Child and Adolescent Psychiatry Clinic with autism (according to DSM-IV-TR criteria) and were enrolled in the study. Symptom severity of the patients was evaluated with a Childhood Autism Rating Scale. Blood samples (EDTA collected) were obtained in order to extract DNA. Whole genome molecular karyotyping analyses were performed with Illumina IScan system by chips, which can scan 330.000 Single Nucleotid Polymorphisms (SNPs) to detect structural anomalies with a 10-kb resolution. All patients had copy number variations (CNV) that sized between 20-kb and 3-Mb. All detected CNVs were analyzed by the help of KaryoStudio software and DGV database. The ones which might be causal and pathogenic were selected. Pathogenic CNVs (7 deletions, 2 duplications) were detected in 9 patients (29%). As a result, this is the first study whereby a molecular karyotyping technique was successfully used in autism patients in Turkey. Moreover, an intermediate resolution of 330.000 SNP chips were proven to be efficient for molecular karyotyping analysis.

Effects of single nucleotid polymorphisms in VEGFR2 on shear stress activated endothelial cells

Effects of single nucleotid polymorphisms in VEGFR2 on shear stress activated endothelial cells

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

A large number of studies have examined associations between brain-derived neurotrophic factor (BDNF) gene polymorphisms and depressive symptoms. However, results still remain controversial. Recent studies suggested a significant age and gender effect on the heritability of depression. The potential neurobiological pathways that could possibly mediate this relationship have not been examined so far. Since BDNF is involved in the regulation of neurotransmitter production, a mediating role of neurotransmitters seems plausible. The present study aims to examine the association between three common BDNF single-nucleotid polymorphisms (SNPs; rs7103411, rs7124442, and rs6265) and depressive symptoms in a community-based elderly population taking into account the serum levels of four neurotransmitters, serotonin, dopamine, adrenalin, and noradrenalin, as potential mediating factors. We also examined whether age and gender had a modifying effect on this association. We collected and analyzed the genetic and laboratory data as well as Center for Epidemiologic Studies-Depression scores of 350 community-dwelling elderly individuals (aged 65+ years). We found that the BDNF rs6265 polymorphism was related to the severity of depressive symptoms, and that this association was independent of neurotransmitter levels. Stratified analyses showed that this association was restricted to older individuals (≥74 years) and men. The associations of SNPs rs7103411 or rs7124442 SNP with depressive symptoms were not statistically significant. This study importantly adds to the existing literature by affirming previous assumptions on an age and gender difference in the relation between BDNF genotype and depression. We moreover first-time report a missing mediating role of neurotransmitters in this association.

Sodium channels of SCNIA gene mutations in generalized epilepsy with febrile seizure plus (GEFS+) spectrum related to autism

Background Mutations in the a-subunit of the first neuronalsodium channel gene SCNIA have been demonstrated forgeneralized epilepsy \\lith febrile seizures plus (GEFS+), severemyoclonic epilepsy in infancy (SMEI), and borderline SMEI(SMEB). SCNIA mutations are also described in patients 'Withpsychiatric disorders such as autism.Objective To identify the mutations of SCNIA gene in patientswith GEFS+ spectrum which may be related to autism.Methods We examined four patients v.ith autism and GEFS+spectrum who were admitted to the Department of Child Health,Sardjito Hospital, Yogyakarta, Indonesia. Diagnosis of autism wasbased on DSM􀁟IV;ICD X criteria. Mutations in SCNIA wereidentified by PCRamplification and denaturing high􀁟performanceliquid chromatography analysis, Mth subsequent sequencing.Results There were four patients, all boys, aged 1.8 year to 7 years.The phenotypes of epilepsy were GEFS+ in one patient, SMEBin one patient and SMEI in two patients. Sequencing analysisrevealed a G􀁟to􀁟A heterozygous transition which was detectedat nucleotide c.4834G&gt;A (p.V1612I ) in exon 25. Other singlenucleotid polymorphisms (SNPs) were c.383 +66T&gt;C in intron 2,c.603-91G&gt;A and c.603-1060&gt; T in intron 4, c.965-21C&gt; T inintron 6, c.1028+21T&gt;Cin intron 7, c.2173G&gt;A in exon 12 andc. 2177-38C&gt;A, c.2177-12delT, c.2176+44C&gt; T in intron 12.Conclusion In this study, we reported the first cases Mth mutationin SCNIA gene in GEFS+ spectrum related to autistic patientsin Indonesian population, which showed a missense mutationp.V16121. [Paediatr lndones. 2010;50:125-32].

Brain imaging as a diagnostic tool in clinical practice?

Based on the sound knowledge of clinical psychiatry neuroscientists embark since over 20 years to discover the biological bases of mental disorders. Whereas the “window to the brain” was firstly dominated by neuroendocrine and biochemical models, we now have the possibility to use sophisticated brain imaging techniques which span from electrophysiology to techniques derived from nuclear medicine. Furthermore, the combination of brain imaging techniques with genetic variables promises to have a close insight into brain-environment interactions. For treatment of psychiatric diseases, multidimensional criteria for selection of a psychotropic medication is necessary to not only judge the clinical phenotype but also the functional phenotype and finally the genotype. Whereas the clinical phenotype is characterized by psychiatric syndromes including psychiatric and somatic comorbidity, the functional phenotype can be uncovered with neuroendocrine measurements, sleep physiology, imaging techniques as well as proteomics. Finally, the genotype can be characterized by single nucleotid polymorphisms (SNP), coupling as well as the determination of candidate genes. Imaging genetics is a new way to achieve insight in the genetic variables of changes on a cellular level which thereafter influence information processing and finally are represented in complex functional interaction of human behavior. Based on this knowledge it is evident that psychiatrists not only should be determined to the clinical symptomatology of their patients but also on the underlying biological processes which can in turn be influenced to various degress with pharmacological as well as non-pharmacological treatment modalities, since the brain has a specified way to get better.

Complete rRNA Gene Sequences Reveal that the Microsporidium Nosema bombi Infects Diverse Bumblebee (Bombus spp.) Hosts and Contains Multiple Polymorphic Sites

Characterisation of microsporidian species and differentiation among genetic variants of the same species has typically relied on ribosomal RNA (rRNA) gene sequences. We characterised the entire rRNA gene of a microsporidium from 11 isolates representing eight different European bumblebee (Bombus) species. We demonstrate that the microsporidium Nosema bombi infected all hosts that originated from a wide geographic area. A total of 16 variable sites (all single nucleotid polymorphisms (SNPs)) was detected in the small subunit (SSU) rRNA gene and 42 (39 SNPs and 3 indels) in the large subunit (LSU) rRNA sequence. Direct sequencing of PCR-amplified DNA products of the internal transcribed spacer (ITS) region revealed identical sequences in all isolates. In contrast, ITS fragment length determined by PAGE and sequencing of cloned amplicons gave better resolution of sequences and revealed multiple SNPs across isolates and two fragment sizes in each isolate (six short and seven long amplicon variants). Genetic variants were not unique to individual host species. Moreover, two or more sequence variants were obtained from individual bumblebee hosts, suggesting the existence of multiple, variable copies of rRNA in the same microsporidium, and contrary to that expected for a class of multi-gene family under concerted evolution theory. Our data on within-genome rRNA variability call into question the usefulness of rRNA sequences to characterise intraspecific genetic variants in the Microsporidia and other groups of unicellular organisms.

Identification of new single nucleotid polymorphisms (SNP) in alcohol dehydrogenase class IV ADH7 gene within a French population

Many epidemiological studies have explored the possible link between the susceptibility to alcohol related cancers, such as oesophageal cancers, and genetic variants of alcohol dehydrogenases (ADHs). Alcohol dehydrogenase class IV ADH7 is mainly expressed in the upper aero-digestive tract and is involved in the first pass ethanol metabolism. As far as we know, no study has described single nucleotide polymorphisms (SNPs) within ADH7 exons in the Caucasian population. Therefore, in a pilot study, we used the denaturing high performance liquid chromatography (DHPLC) method to screen 49 oesophageal cancer cases for SNPs in the ADH7 gene. A total of 5 SNPs was observed in this study: one SNP in the 5' non-translated regions of exon 1, two SNPs in introns 3 and 4 and two others SNPs in exons 3 and 4. The SNP located in the exon 1, which has never been described before, occurred in a reverse TATA box whereas the SNP of exon 3 was a non-silent polymorphism. Because these two SNPs could potentially affect the transcription and/or the enzyme activity, their distribution was evaluated in a representative sample of healthy Caucasians (n = 89) recruited in Lower Normandy. Frequencies of heterozygous samples ranged from 11% (exon 3) to 28% (exon 1). No homozygous samples were found. In this pilot study, the DHPLC method was suitable for both SNP screening and genotyping and allowed the detection of five SNPs in the ADH7 gene, two of which have never been described before, among the European population.

Alpha-1-Antitrypsin Levels and Genetic Variation of the Alpha-1-Antitrypsin Gene in Peyronie’s Disease

Alpha-1-antitrypsin (alpha1-antitrypsin) is a major protease inhibitor controlling tissue degradation. Reduced alpha1-antitrypsin levels could result in a change of collagen metabolism. Previous studies have described decreased alpha1-antitrypsin levels in patients with Peyronie's disease. However, only a small number of patients were analyzed, and the reason for the decreased alpha1-antitrypsin levels remained unclear. This study investigated prospectively the levels of alpha1-antitrypsin in patients with Peyronie's disease, as well as genetic variation in the coding region of the alpha1-antitrypsin gene. Alpha1-antitrypsin levels were determined prospectively in 94 patients with Peyronie's disease and compared to healthy controls. Analysis of the alpha1-antitrypsin gene (S, Z variants; single nucleotid polymorphisms [SNPs]: T-395A, M2, M3, G6118A) was done in 141 Peyronie's patients including 43 patients with investigated alpha1-antitrypsin serum levels and compared to healthy controls. In patients with Peyronie's disease, the alpha1-antitrypsin levels seemed to be decreased significantly compared to healthy controls. However, in the age matched approach no significant differences occurred. Moreover, a significant (p < 0.002) decrease of the alpha1-antitrypsin level with increasing age was observed, explaining the initial differences between the two groups. In confirmation with these findings, no significant association of the alpha1-antitrypsin gene variants with Peyronie's disease was detectable. The results of this study do not indicate a significant association between Peyronie's disease and decreased alpha1-antitrypsin levels. Low alpha1-antitrypsin levels in Peyronie's patients are, rather, an age-related phenomenon, as revealed by the comparison with aged matched healthy controls. The decrease of the alpha1-antitrypsin serum level with increasing age has not been described before.

Polymorphism of Na+/Ca2+ exchanger gene and antihypertensive response to calcium channel blockers in patients with essential hypertension

The myocardial Na+/Ca2+ exchanger (NCX) plays an important role in the regulation of cardiac contractility, and the effects of calcium channel blockers (CCBs) on the heart is based upon regulating Ca2+ influx transient amplitudes. We investigated the role of genetic variance of NCX-1 gene ( NCX-1) in the antihypertensive response to CCBs in patients with essential hypertension. Study subjects were 165 patients (male 81, female 84; 65.±9.6 years old) with essential hypertension who were newly prescribed CCBs. All of them were given a written informed consent. We performed direct sequence all region of exon, promotor and part of intron of NCX-1. In consequence, we detected 15 polymorphisms including 13 single nucleotid polymorphisms (SNPs). We chose 7 SNPs, which allele frequency was above 5%. Response to CCBs was evaluated as the difference in three consecutive measurements of mean blood pressure before and after administration of CCBs. Only C/T polymorphism in intron 1d (db SNP ID: rs2301340) showed significant correlation with the antihypertensive effect of CCB. The frequency of genotypes were CC 91%, CT 9% and TT 0%. Average declines in mean blood pressure was 9.5.±0.9mmHg in patients with C allele and 16.7±2.6mmHg in patients with T allele (p=0.01). After divided patients into two groups based on good responder (Response to CCBs more than 5 mmHg) and non-responder (Response to CCBs less than 5 mmHg or unchanged), frequency of T allele was significantly higher than that of C allele (p=0.04). Assessment of polymorphism in NCX-1 may help to identify hypertensive patients who are responsive to CCBs therapy.

Study on possible correlations between coagulation-related single nucleotid polymorphisms in patients with venous and arterial thromboembolism

Study on possible correlations between coagulation-related single nucleotid polymorphisms in patients with venous and arterial thromboembolism

Flow-mediated dilatation in human circulation: diagnostic and therapeutic aspects

a disturbance of endothelial function is considered as a key event in the development of atherosclerosis ([63][1]). Thus reliable assessment of endothelial function in humans appears highly desirable. With respect to the major endothelial functions, this aim can be achieved by different approaches: