Receptor Polymorphisms In Patients Research Articles

TAS2R38 Bitter Taste Receptor Polymorphisms in Patients with Chronic Rhinosinusitis with Nasal Polyps Preliminary Data in Polish Population.

Chronic rhinosinusitis (CRS) affects 5-12% of the general population, and the most challenging patients are those with nasal polyposis (CRSwNP). Its complexity, unpredictability, and difficulties in selecting a treatment plan individually for each patient prompted scientists to look for possible genetic causes of this disease. It was proven that single nucleotide polymorphisms (SNPs) in the TAS2R38 gene may affect the mobility and the activity of the ciliated epithelium of the upper respiratory tract what can contribute to individual differences in susceptibility to CRS. There are two common haplotypes: a "protective" type (PAV), and a "non-protective" type (AVI). CRS patients who are homozygous PAV/PAV are considered as less susceptible to the severe course of the disease, whereas patients with AVI/AVI haplotype are more vulnerable. The aim of this study was to examine TAS2R38 gene polymorphisms among CRSwNP patients and control group (N = 544) with the evaluation of the association between the distribution of studied polymorphic variants and the incidence as well as severity of CRSwNP in the study group. Whole blood samples from CRSwNP patients (N = 106) and the control group (N = 438) were analyzed for alleles of the TAS2R38 gene using real-time PCR single nucleotide polymorphism genotyping assays for rs713598, rs1726866, and rs10246939. PAV (SG: 41%; CG: 49%) and AVI (SG: 59%; CG: 51%) haplotypes were the only ones detected in the study. The AVI haplotypes were 1.5 times more frequent in the study group than in the control group (p = 0.0204; OR = 1.43). AVI/AVI individuals tended to have more severe symptoms in the VAS scale, less QoL in the SNOT-22 test, and a bigger nasal obstruction upon endoscopic examination. Patients with PAV/PAV were twice more likely to have minor changes in preoperative CT scans (p = 0.0158; OR = 2.1; Fi = 0.24). Our study confirmed that the PAV/PAV diplotype might have some protective properties and carrying the AVI haplotype might predispose to the development of CRSwNP.

FC gamma receptor polymorphisms in patients with immune thrombocytopenia

ABSTRACTIntroduction: Immune thrombocytopenia (ITP) is an autoimmune blood disease of unknown etiology. The aim of our study was to investigate a possible role of FCGR2A and FCGR3A polymorphisms in the development of primary ITP.Methods: We analyzed 125 adult patients with ITP and 120 healthy controls. Genotyping was performed by using PCR-RFLP methods.Results: Our results showed significantly higher frequency of high-affinity FCGR3A-158V allele in patients with ITP compared with control subjects (47.2% versus 37.5%; p = 0.037). We did not find significant differences in the genotype distribution or allele frequencies for FCGR2A-131H/R between patients and controls, p = 0.652 and p = 0.478. In the groups of patients with unresponsive and responsive ITP we found significantly different genotype distribution and allele frequencies for FCGR3A, p = 0.036 and p = 0.008 respectively. There was no significant difference in genotype and allele frequencies for FCGR2A between these two groups of patients. Our results confirmed that the combination of high-affinity FCGR2A-131H and FCGR3A-158V allele was more common in patients with ITP than in controls (55% versus 40%; p = 0.024).Conclusion: Our results suggest possible role of FCGR3A polymorphism in the etiology, development and clinical outcome of ITP, but larger prospective studies are needed to confirm these results.

Fcγ receptor polymorphisms in patients with transient hypogammaglobulinemia of infancy presenting with mild and severe infections.

Patients with transient hypogammaglobulinaemia of infancy (THI) may have mild infections or be asymptomatic. About 20% of THI patients have very severe and recurrent infections and receive intravenous immunoglobulins (IVIg) for replacement therapy and infection prophylaxis. It is still not clear why some THI patients are severely symptomatic; it has been suggested that there might be additional immunologic or environmental factors or other co-morbidities. As an immunological factor, Fcγ receptor polymorphisms (H/H-131, H/R-131 and R/R-131 for FcγIIa; V/V-158, V/F-158 and F/F-158 for FcγRIIIa; NA1/NA1, NA1/NA2 and NA2/NA2 for FcγRIIIb) were analysed in THI patients who had very severe infections and need hospitalisation (treated with IVIg) (n:18) and in THI patients who were asymptomatic or had mild infections (treated with antibiotics or received no medication) (n:25). Genotypic distributions between two groups did not deviate significantly from the Hardy-Weinberg equilibrium expectations (p > 0.05) and odds ratios for "disease risk estimate" did not show any dominance for any genotype. Allele frequencies did not show any significant difference between the two groups (p >0.05). The number of infections per year for each Fcγ receptor genotype was not significantly different between both groups. There is no association between the heterogeneous clinical picture of THI patients and Fcγ receptor gene polymorphisms.

964: FokI and TakI vitamin D receptor polymorphism in patients with prostate cancer

964: FokI and TakI vitamin D receptor polymorphism in patients with prostate cancer

Fractalkine Gene Receptor Polymorphism in Patients With Multiple Sclerosis

ABSTRACTBackground: Although the immunopathogenesis of multiple sclerosis (MS) has been intensely investigated in recent years, some associated molecules still have not been examined. For instance, no study has been conducted to investigate a possible polymorphism in the fractalkine receptor gene. Methods: In order to examine fractalkine gene receptor polymorphisms, 3 mL of serum from 92 MS patients and 91 controls were stored at −20°C. DNA was extracted from the serum samples that were purified, and the gene regions in CX3CR1 (i.e., the fractalkine regions) containing the T280M and V294I fractalkine receptor haplotypes were amplified via the polymerase chain reaction (PCR) technique. The obtained fragments were then cut using restriction enzymes, and agarose gel electrophoresis was performed. Results: In a comparison of the patients and controls, we found that the median values of the Expanded Disability Status Scale (EDSS) scores among genotypes of the V294I polymorphism in the fractalkine gene receptor were statistically higher in genotype II than genotype VI. Also, relapsing/remitting MS (RRMS) was statistically higher in genotype VI than in genotype II, whereas the frequency of secondary progressive MS (SPMS) was statistically higher in genotype VV than in the genotype VI for the same polymorphism. Conclusions: Although many polymorphism studies have focused on patients with MS, there is no polymorphism study about the fractalkine receptor which is a chemokine and plays an important role in neuroinflammation and neurodegeneration. Our results provide information about disease progression and may also be beneficial in developing new strategies for the treatment of the disease.

Vitamin D receptor polymorphisms in patients with cutaneous melanoma

Vitamin D receptor polymorphisms in patients with cutaneous melanoma

Analysis of β1 and β2-adrenergic receptors polymorphism in patients with apical ballooning cardiomyopathy

Objective The aim of our study was to analyse the frequency of β1 and/or β2 adrenergic receptor polymorphisms in patients with takotsubocardiomyopathy (TTC).Methods and resultsβ1 and/or β2 adrenergic receptor polymorphisms in 61 patients with TTC were compared with 109 controls. The β1 adrenoreceptor (amino acid position 389) genotype frequencies were signifi cantly diff erent in the two groups; assuming a recessive model for the allelic variant coding for Arg on this position, the odds ratio was 3.14, 95% CI 1.55-6.37 (P= 0.0015). The β2 adrenoreceptor amino acid position 27 genotype was signifi cantly diff erent and assuming a recessive model for the allelic variant coding for Gln on this position, the odds ratio was 0.29, 95% CI 0.12-0.74 (P= 0.009).Conclusions This study showed for the fi rst time an association between TTC phenotype and β1 adrenoreceptor gene polymorphisms. Beta adrenoreceptors gene polymorphisms are probably disease modifi ers, and any risk estimate should be based on a combination of genotypes and on interactions with other genes and environmental features.

The growth hormone receptor polymorphism in patients with acromegaly: relationship to BMI and glucose metabolism

The aim of this study was to investigate association between the frequencies of Growth Hormone receptor (d3GHR) gene polymorphisms and some clinical parameters of acromegalic patients. Total of 35 acromegalic patients were enrolled to study. The d3GHR polymorphism was identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose (FPG), Fasting insulin, HOMA-IR, IGF-I, GH, IGFBP3, triglyceride, HDL and LDL cholesterol concentrations were evaluated. The frequencies of d3GHR genotypes were found as follows; 5 (14.3%) subjects had d3/d3, 11 (31.4%) had d3/fl and 19 (54.3%) had fl/fl in patients. The prevalence of the d3 and fl alleles was 30 and 70%, respectively. Systolic blood pressure, fasting insulin and HOMA-IR was found significantly increased in homozygote d3GHR genotype group compared to d3/fl subjects (P < 0.05). In addition, BMI was observed significantly different among three genotypes (P = 0.007) and in the subjects with d3/d3 genotype, BMI was found significantly higher than d3/fl and fl/fl genotypes groups. As well as, no significant difference was found between the d3 and fl alleles group in terms of the clinical parameters except for BMI (P = 0.002). It can be said that the d3GHR gene polymorphism may affect BMI, systolic blood pressure and insulin regulation. At the same time we can say homozygote d3GHR genotype and d3 allele carriers may have more risk than other genotypes for high BMI.

Vitamin D receptor polymorphisms in patients with cutaneous melanoma

The vitamin D receptor (VDR) gene has been associated with cancer risk, but only a few polymorphisms have been studied in relation to melanoma risk and the results have been inconsistent. We examined 38 VDR gene single nucleotide polymorphisms (SNPs) in a large international multicenter population-based case-control study of melanoma. Buccal DNAs were obtained from 1,207 people with incident multiple primary melanoma and 2,469 with incident single primary melanoma. SNPs with known or suspected impact on VDR activity, haplotype tagging SNPs with ≥ 10% minor allele frequency in Caucasians, and SNPs reported as significant in other association studies were examined. Logistic regression was used to calculate the relative risks conferred by the individual SNP. Eight of 38 SNPs in the promoter, coding, and 3' gene regions were individually significantly associated with multiple primary melanoma after adjusting for covariates. The estimated increase in risk for individuals who were homozygous for the minor allele ranged from 25 to 33% for six polymorphisms: rs10875712 (odds ratios [OR] 1.28; 95% confidence interval (CI), 1.01-1.62), rs4760674 (OR 1.33; 95% CI, 1.06-1.67), rs7139166 (OR 1.26; 95%CI, 1.02-1.56), rs4516035 (OR 1.25; 95%CI, 1.01-1.55), rs11168287 (OR 1.27; 95%CI, 1.03-1.57) and rs1544410 (OR 1.30; 95%CI, 1.04-1.63); for two polymorphisms, homozygous carriers had a decreased risk: rs7305032 (OR 0.81; 95%CI 0.65-1.02) and rs7965281 (OR, 0.78; 95%CI, 0.62-0.99). We recognize the potential false positive findings because of multiple comparisons; however, the eight significant SNPs in our study outnumbered the two significant tests expected to occur by chance. The VDR may play a role in melanomagenesis.

β2-Receptor Polymorphisms in Patients Receiving Salmeterol with or without Fluticasone Propionate

Retrospective pharmacogenetic studies have questioned whether patients with asthma who are arginine homozygous at the beta(2-)adrenergic receptor (position 16) should use long-acting beta-agonists. To examine whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by beta- receptor polymorphisms. Subjects using only as-needed albuterol were screened and completed two sequential open-label run-in periods (8 wk on as-needed albuterol; 8 wk on as-needed ipratropium). Five hundred forty-four subjects were randomized by Arg16Gly genotype to salmeterol alone or with fluticasone propionate for 16 weeks. Change from baseline in morning peak expiratory flow was the primary endpoint. Lung function responses were sustained over treatment and no statistically significant changes from baseline between genotypes within treatments were observed. Overall mean changes in morning peak flow for salmeterol with fluticasone propionate were 32.6 L/min (Arg/Arg vs. Gly/Gly, 95% confidence interval [CI], -6.3, 22.1), 25.9 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -7.1, 21.3), and 24.9 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -13.0, 14.6), and for salmeterol alone were 19.4 L/min (Arg/Arg vs. Gly/Gly, 95% CI, -1.7, 21.4), 24.6 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -13.0, 10.6), and 12.4 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -0.2, 22.3) for Arg/Arg, Arg/Gly, and Gly/Gly genotypes, respectively. Other measures of asthma control showed similar responses. The results showed no evidence of a pharmacogenetic effect of beta-receptor variation on salmeterol response. Clinical trial registered with www.clinicaltrials.gov (NCT 00102882).

Adrenergic receptor polymorphisms in patients with stress (tako-tsubo) cardiomyopathy

Stress (tako-tsubo) cardiomyopathy (SC) is a newly reported condition afflicting older women, characterized by acute left ventricular (LV) systolic dysfunction, triggered by emotionally and physically stressful events, and occurring without significant coronary obstruction. Sympathetic nervous system hyperactivity has been implicated in the pathophysiology of SC. Single nucleotide polymorphisms involving the adrenergic receptors (AR) might result in susceptibility to SC. Forty-one female SC patients were identified aged 34-89 years (mean 65) and were compared with 43 control females of similar age with respect to AR genotype frequencies for B1 receptor (amino acid positions 389 and 49) and alpha 2c receptor (deletion 322-325). For SC patients, initial LV ejection fraction was 32 ± 10% vs. 62 ± 11% in control patients, p < 0.05. Genotype frequencies for SC patients vs. controls were B1 389 Arg/Arg (0.49 vs. 0.51), B1 389 Arg/Gly (0.49 vs. 0.49), B1 389 Gly/Gly (0.02 vs. 0), B1 49 Ser/Ser (0.88 vs. 0.81), B1 49 Ser/Gly (0.12 vs. 0.16), B1 49 Gly/Gly (0 vs. 0.02), alpha 2c Wt/Wt (0.93 vs. 0.86), and alpha 2c Wt/Del 322-325 (0.07 vs. 0.14); p = ns for all comparisons. Genotype polymorphism frequencies for B1 receptor (amino acid positions 389 and 49) and alpha 2c receptor (deletion 322-325) are not significantly different in SC patients compared to female controls. These data suggest that these AR polymorphisms do not mediate the sympathetic nervous system hyperactivity in SC patients.

P2Y12 polymorphisms and antiplatelet effects of aspirin in patients with coronary artery disease

* Genetic polymorphisms of the P2Y(12) ADP receptor on platelets have been shown to contribute to variability in platelet aggregation in healthy humans. * P2Y(12) ADP receptor polymorphisms are more frequently present in patients with vascular disease than in healthy people. * The majority of patients with vascular disease receive acetylsalicylic acid as an anti-aggregatory agent, which has also been shown to induce a variable response; however, the role of P2Y(12) ADP receptor polymorphisms in the platelet response to acetylsalicylic acid in patients with vascular disease has not yet been studied. * The present data show that the platelet response to acetylsalicylic acid is independent of the presence or absence of P2Y(12) ADP receptor polymorphisms in patients with stable coronary artery disease who have had their first myocardial infarction. * This is important, as studies in healthy humans had suggested that carriers of P2Y(12) ADP receptor polymorphisms may be at increased risk of experiencing cardiovascular events. * However, the observed variability of the platelet response to the cyclooxygenase inhibitor acetylsalicylic acid (in our study) and to the P2Y(12) ADP receptor blocker clopidogrel (in a study by Angiolillo et al) in patients with coronary artery disease is clearly not determined by common P2Y(12) ADP receptor polymorphisms. Recently, two genetic polymorphisms of the platelet ADP receptor P2Y(12) (haplotypes H2 and 34T) have been implicated in increased platelet aggregation and atherothrombotic risk. It was suggested that these polymorphisms contribute to a diminished response to antiplatelet drugs. Therefore, we investigated the effects of these polymorphisms on platelet aggregation in aspirin-treated patients with coronary artery disease (CAD). Platelet aggregation was studied in platelet-rich plasma from 124 patients with CAD treated with 100 mg aspirin day(-1). P2Y(12) ADP receptor polymorphisms were determined by PCR-RFLP. The 52G > T polymorphism was used as tag-SNP for the H2 haplotype. Aggregation was induced by 1 mg l(-1) collagen. In a subgroup (n = 72), a concentration-response curve to collagen (0.5-10 mg l(-1)), aggregation at 2 micromol l(-1) ADP and 1 mmol l(-1) arachidonic acid were determined. Whereas arachidonic acid-induced aggregation was inhibited in all patients, collagen and ADP-induced aggregation were highly variable. However, aggregation did not differ significantly between carriers and noncarriers of the 52T-allele (1 mg l(-1) collagen: 32.7% (21.9-38.6%) vs. 32.5% (21.2-41.6%); P = 0.77; ADP: 33.1% (29.9-40.9%) vs. 39.1% (31.5-49.7%); P = 0.34), respectively. EC(50) values were 1.26 mg l(-1) (0.79-2.02) and 1.54 mg l(-1) (0.98-2.4) collagen in noncarriers and carriers of the H2 haplotype, respectively (P = 0.56). Moreover, the 34 degrees C > T polymorphism did not significantly affect any of the aggregatory responses. Low-dose aspirin inhibits platelet aggregation to the same extent in patients carrying or not carrying the P2Y(12) H2 haplotype and/or the 34T allele. Our data do not support the hypothesis that these polymorphisms contribute to an attenuated antiplatelet effect of aspirin.

Su.85. Assessment of Chlamydia Pneumoniae Dnaemia and Toll-Like Receptor Polymorphisms in Patients with Acute Myocardial Infarction

Su.85. Assessment of Chlamydia Pneumoniae Dnaemia and Toll-Like Receptor Polymorphisms in Patients with Acute Myocardial Infarction

IgG- Fcγ- receptor polymorphisms in drug-induced-induced agranulocytosis

The pathomechanisms of clozapine-induced agranulocytosis are considered controversial, immune and/or toxic mechanisms are favoured (1)To further examine the immunogenetic hypothesis of clozapine-induced agranulocytosis we performed genotyping of IgG Fcγ receptor polymorphisms in patients suffering from agranulocytosis induced by clozapine (N=49), ticlopidine (N=11) thyreostatics (N=8) other drugs (N=12) and controls (n=75). Fcγ receptors are protective for antigens by forming an antigen antibody complex, and are located on the surface of macrophages, neutrophils and natural killer cells. The responsible gene is located on chromosome 1q23-q24. Genotyping included examination of polymorphisms of RIIA (associated to heparine –induced thrombocytopenia), RIIB (activation of NADPH-oxidase) and RIIIB-receptors (located on neutrophil granulocytes). We did not find statistically different distribution of polymorphisms between patients and controls.

Odorant receptor polymorphisms in patients with non-allergic vasomotor rhinitis

Rationale Non-allergic vasomotor rhinitis (VMR) is a common clinical condition where prick-skin-test negative patients experience nasal congestion and post-nasal drainage after exposure to a spectrum of irritants and barometric/temperature changes. The mechanism(s) for this disorder is(are) unknown but are commonly triggered by olfaction. Because odorant receptor gene ( OR) polymorphisms have previously been reported, implying inter-individual variation in olfactory response, we examined whether OR genes were associated with the VMR phenotype. Methods Genomic DNA was extracted from 30 VMR patients (Ave.age=23 ; F :M=2 :1; Cauc :AfrAm=28 :2) and 58 parents (Ave.age=43 ; Cauc :AfrAm=54 :4 ; two patients had the same parents) using the GenomicPrep ™ DNA isolation kit. We used a candidate-gene-region approach to examine polymorphisms in OR gene cluster I (4.43 Mb) and cluster II (1.99 Mb) located on chromosome (Chr) 11 and the MHC region (4.1 Mb) located on Chr 6 as a control. The case-control and transmission disequilibrium tests were used to identify phenotype-genotype associations. Results Two highly statistically significant single-nucleotide polymorphisms (SNPs) in the Chr 11@52 OR Cluster I region were associated with the VMR phenotype adjacent to one another 178 kb apart (P=.004 and .02). Two SNPs ( P=.016) located in the OR Cluster II region and two other adjacent SNPs ( P<.05) in OR Cluster I were also statistically significant. No significant markers were found among the 15 single tandem repeats used to screen the MHC region—commonly associated with allergic disorders. Conclusions These preliminary data suggest important phenotype-genotype associations between VMR and OR genes might exist warranting further investigation.

Beta-adrenergic receptor polymorphisms in patients with elevated factor VIII levels with venous thrombosis.

Beta-blockers significantly reduce elevated factor VIII (FVIII) levels in patients with venous thromboembolism (VTE). To determine whether beta-adrenergic receptors are important in the aetiology of high FVIII levels, we investigated four coding polymorphisms of the beta1- and beta2-receptor genes in 64 patients with high FVIII and VTE and 100 healthy controls. Genotypic and allelic frequencies were not significantly different between the patient and control groups. However, a significant dosage effect of the beta2 E27 allele on plasma FVIII coagulant activity levels was observed in normal group O individuals.

Relationship between adverse effects of antipsychotic treatment and dopamine D(2) receptor polymorphisms in patients with schizophrenia.

Extrapyramidal adverse symptoms (EPS) represent a major type of adverse events in treatment with typical antipsychotic drugs which share high affinity to the dopamine D(2) receptor (DRD2). Genetic variants of this receptor may modulate the therapeutic response and the severity of adverse symptoms of antipsychotics. We analyzed nine known polymorphisms of the DRD2 in 665 schizophrenic patients with European Caucasian ethnic background and compared the intensity of acute dystonia, extrapyramidal symptoms, akathisia, and tardive dyskinesia between carriers of different DRD2 genotypes. In a subgroup of 40 patients with most severe extrapyramidal symptoms we sequenced the coding region including the exon-intron junctions of the DRD2 gene. Functionally relevant DRD2 amino acid variants (Ser(310), Cys(311)) were rare or were not found at all (Ala(96)). Complete sequence analysis of sufferers from the most severe adverse effects revealed two new intronic polymorphisms and a silent polymorphism in exon 7, but no new amino acid variants beyond those which are already known. We found no significant association between these polymorphisms and the intensity of the different types of adverse neurologic effects of the antipsychotics. These results were obtained by correlating adverse events with each of the nine single nucleotide polymorphisms and by correlation with the estimated haplotypes. In conclusion, genetic variations in the DRD2 gene were no major predictors of the individually variable adverse effects from antipsychotic treatment in Caucasian schizophrenic patients.

Molecular characterisation and racial distribution of androgen and vitamin D receptor polymorphisms in patients with prostate cancer, benign prostatic hyperplasia and age-matched healthy controls.

Molecular characterisation and racial distribution of androgen and vitamin D receptor polymorphisms in patients with prostate cancer, benign prostatic hyperplasia and age-matched healthy controls.

Class II human leukocyte antigen genes and T cell receptor polymorphisms in patients with rheumatoid arthritis

Human leukocyte antigen (HLA) typing was performed in 174 patients with rheumatoid arthritis and 222 white control subjects. Increases in HLA-DR4 and HLA-DR1 were observed as in previous studies. Each of these appeared to be inherited as dominant risk factors. Southern blotting with a DR-beta probe after digestion of genomic DNA with the restriction enzyme Bam HI showed seven bands. Three of them correlated with DR4 and were increased in rheumatoid arthritis patients. Subsets of DR4 were determined by polymerase chain reaction amplification followed by hybridization with oligonucleotide probes. Dw4 was increased in rheumatoid arthritis patients, and the frequency of the other subsets appeared to be similar in rheumatoid arthritis patients and control subjects. A polymorphism associated with the T cell receptor V-beta-8 gene family was significantly increased in rheumatoid arthritis patients.