控释硝苯地平降压效应谷／峰比率的临床研究

目的　探讨计算控释硝苯地平治疗原发性高血压患者降压效应谷/峰比率（T/　PR）的最佳方法和该药的平稳指数(SI)　。方法　轻、中度原发性高血压患者32例,每天早晨服控释硝苯地平(nifedipine　GITS)　30　mg,治疗前及4　wk后作动态血压监测,分别以2　h个体法和整组法计算T/PR并计算该药的SI　。结果　4　wk治疗后患者偶测血压和动态血压的降低幅度分别为(24±12)/(12±8)　mmHg和(14.5±3.9)/(11.2±3.1)　mmHg;　个体法计算的收缩压和舒张压的T/PR分别为0.65±0.23和0.66±0.25,　而整组法则分别为0.62和0.68;　该药的收缩压和舒张压SI分别为3.74和3.77　。结论　控释硝苯地平可24　h有效平稳地降压;其降压平稳作用可通过T/PR和SI反映。     

Renin-angiotensin-aldosterone system gene polymorphisms and antihypertensive response to irbesartan in Chinese hypertensives

The aim of this study was to determine whether specific single nucleotide polymorphisms (SNPs) and their reconstructed haplotypes in renin-angiotensin-aldosterone system (RAAS) genes were associated with antihypertensive reduction to irbesartan treatment. Thousand one forty-two hypertensives were recruited and received 150 mg irbesartan daily for 4 weeks. Blood pressures (BPs) and blood samples, at postdose on the 28th day, were measured. Predose BPs and plasma irbesartan concentrations were also measured. Involved SNPs in RAAS pathway genes were genotyped. Genotype (-344 TC) in the CYP11B2 had a significantly greater systolic blood pressure (SBP) reduction versus the TT genotype (p = 0.001). Subjects with the 174MM genotype of the angiotensinogen (AGT) gene had a significantly greater average SBP reduction (p = 0.025). The C-344T and T1016C polymorphisms in the CYP11B2 gene were both significantly associated with diastolic blood pressure (DBP) reduction (p = 0.026 or p = 0.003). Overall, the three loci-constructed haplotypes of the CYP11B2 gene were associated with DBP reduction (p = 0.008). Haplo-GLM analyses demonstrated that subjects with haplotype CTA had a significantly greater SBP and DBP reductions (p < 0.001 or p = 0.020), whereas subjects with haplotype TAA had a significantly lower SBP and DBP reductions (p < 0.001). Our findings suggested that SNPs and their reconstructed haplotypes in RAAS genes might be involved in the regulation of BP-lowering response to irbesartan in Chinese hypertensives.     

Dopamine transporter gene associated with diminished subjective response to amphetamine.

Individual variability in responses to stimulant drugs may influence risk of stimulant abuse and treatment response. However, the genetic determinants of this variability have yet to be elucidated. The dopamine transporter is an important site of amphetamine action. Therefore, the dopamine transporter gene (DAT1) is a logical candidate gene to study. Using a drug challenge approach, we tested for association between DAT1 genotype and subjective responses to amphetamine in healthy adults. Volunteers participated in a double-blind, crossover design, randomly receiving placebo, 10 mg, and 20 mg oral D-amphetamine, and completed self-report measures on subjective effects including anxiety and euphoria. Subjects were genotyped for the DAT1 3'-untranslated region VNTR polymorphism and divided into groups based on genotype: homozygous for nine repeats (9/9, N=8), heterozygous (9/10, N=36) and homozygous for 10 repeats (10/10, N=52). The effects of amphetamine on ratings of Feel Drug, Anxiety, and Euphoria were examined with ANCOVA. In 9/10 and 10/10 subjects, amphetamine produced its expected effects of increased Euphoria, Anxiety, and Feel Drug (p<0.01). However, in 9/9 subjects, the effects of amphetamine were indistinguishable from placebo, suggesting that the 9/9 genotype has diminished subjective response to acute amphetamine. Interestingly, recent findings also implicate the 9/9 genotype in decreased therapeutic response to the stimulant methylphenidate in ADHD children. The current findings have important implications for understanding the genetic determinants of variability in stimulant response and risk of abuse.     

Monoamine transporter gene polymorphisms affect susceptibility to depression and predict antidepressant response

Rationale  Serotonin transporter (5-HTT) and norepinephrine transporter (NET) are the primary targets of many antidepressants. We aimed to determine the potential correlations of 5-HTT/NET gene polymorphisms with the susceptibility to depression and the antidepressant response to selective serotonin reuptake inhibitors (SSRIs) or dual selective serotonin/norepinephrine reuptake inhibitors (SNRIs). Methods  A total of 579 depressed patients and 437 healthy controls, all of Chinese Han region, were collected and genotyped by polymerase chain reactions (PCR). All patients were under treatment of SSRI or SNRI for 6 weeks, and were evaluated using a 17-item Hamilton Depression Rating Scale (HAMD). Results  Five hundred sixty-seven of 579 patients completed the total treatment, of which 362 were in SSRI and 205 in SNRI group. It was shown that the NET-T182C, interacting with 5-HTTLPR, was associated with the susceptibility to depression. Patients with both NET-T182C C/C and 5-HTTLPR S/S genotypes had lower baseline HAMD scores. Patients with 5-HTTLPR L/L or STin2 12/12 genotype experienced better clinical response to the SSRI treatment. Besides, the STin2 12/12 carriers showed a superior reduction to HAMD scores over treatment period. No correlation between NET T182C/G1287A polymorphisms and antidepressant response was observed. Conclusions  Our study revealed a positive association of the NET-T182C polymorphism with susceptibility to and severity of depression, and a positive association between the 5-HTT polymorphisms and the antidepressant response to SSRI. Combinations of these polymorphisms provided some potential gene–gene interaction effects. These findings might be of some clinical values in optimization of depression treatment. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

河南汉族人群抗高血压药物相关基因多态性与高血压发病及降压效果的关联研究

目的:研究抗高血压药物相关基因多态性在河南汉族人群中的频率分布,并探讨其与高血压发病的相关性,同时评价抗高血压药物基因检测的临床应用价值.方法:选取2019年1-12月郑州市中心医院确诊的526例原发性高血压患者作为高血压组,同时选取100例健康体检者作为对照组.应用PCR-荧光探针法对5类抗高血压药物相关的7个基因多...     

硝苯地平控释片与普通片治疗老年高血压病比较

目的 比较硝苯地平控释片与普通片对老年高血压患者的降压疗效。方法 采用随机、单盲的方法，对８４例老年高血压患者进行２４ｈ动态血压监测，比较其疗效及副反应。结果 两药均能显著降低老年高血压患者的偶测血压及２４ｈ平均血压（Ｐ〈０．０１）。两药在降低偶测压缩压、２４ｈ平均收缩压及白天平均血压幅度方面差异无显著性（Ｐ〉０．０５），硝苯地平控释片能明显降低患者的偶测舒张压（Ｐ〈０．０５）、２４ｈ平均舒张压（     

Multidrug resistance 1 gene polymorphisms are not associated with inflammatory bowel disease and response to therapy in Italian patients

BACKGROUND: Host genetic factors may be important in determining not only disease susceptibility, but also disease behaviour and response to therapy in inflammatory bowel disease. Two polymorphisms (C3435T and G2677T/A) of the multidrug resistance 1 gene have been correlated with the altered P-glycoprotein expression and function in humans, and associated with predisposition to ulcerative colitis and Crohn's disease. AIM: To investigate the contribution of these polymorphisms to disease susceptibility and response to medical therapy. METHODS: A total of 946 inflammatory bowel disease patients (478 Crohn's disease, 272 males, mean age 43 +/- 14 years and 468 ulcerative colitis, 290 males, mean age 48 +/- 15 years) and 450 healthy controls were genotyped for the single nucleotide polymorphisms C3435T and G2677T/A. Patients were also classified on the basis of response to medical therapy (mesalazine, steroids, immunosuppressives and infliximab). RESULTS: Both single nucleotide polymorphisms were in Hardy-Weinberg equilibrium and significant linkage disequilibrium. No significant difference in the allele, genotype, and haplotype frequencies was found in both Crohn's disease and ulcerative colitis patients compared with the controls. No correlation with clinical features was found, except for a reduced frequency of extra-intestinal manifestations in Crohn's disease patients with the G2677T genotype (40%) compared with GG2677 and 2677TT genotypes (54% and 58%, respectively) (P = <0.02). No significant difference was also found after stratifying the patients on the basis of their response to medical therapy. CONCLUSION: The investigated polymorphisms of the multidrug resistance 1 gene have no significant role in disease susceptibility and response to medical therapy in our Italian population of inflammatory bowel disease patients.     

Some dopaminergic genes polymorphisms are not associated with response to antipsychotic drugs in schizophrenic patients

BackgroundTherapeutic effects of all clinically used antipsychotics are related to the reduction of dopaminergic transmission in the limbic system. The aim of present study was two-fold. First, efficacy of atypical drugs (ziprasidone and olanzapine) against schizophrenia symptoms was compared to that offered by a typical antipsychotic medication, perazine. Second, associations between some dopaminergic genes polymorphisms and therapeutic response to antipsychotics were assessed in the same group of schizophrenia patients.MethodsOne hundred ninety one Caucasian patients admitted with exacerbation of paranoid schizophrenia were genotyped for polymorphisms of the DRD2 [the ins/del -141C (rs1799732) and exon 8 (rs 71653615)], DRD2/ANKK1 Taq IA (rs 1800497), DAT1 (the 40 bp VNTR), COMT (rs 4680), and MAOA gene (the 30 bp VNTR in promoter). The patients were randomly assigned to the treatment with perazine, olanzapine or ziprasidone givenasmonotherapy for 3 months. Treatment efficacy was measured from baseline (T0) to T1 (14 days) and T2 (3 months). A retention rate was also assessed at T1 and T2.ResultsThe three antipsychotics did not differ in terms of reduction of the PANSS score or retention rate at the follow-up. There was no interaction between the investigated polymorphisms and response to the antipsychotic treatment.ConclusionsThe present results suggest that: i) there are no major differences in short-term efficacy or effectiveness of atypical (olanzapine, ziprasidone) and typical (perazine) antipsychotic drugs; ii) the studied polymorphisms are not primarily involved in treatment response to antipsychotics in schizophrenia patients.     

依那普利联合硝苯地平控释片治疗高血压疗效观察

目的观察依那普利联合硝苯地平控释片治疗高血压病的临床疗效。方法将120例高血压患者随机分为治疗组和对照组各60例。对照组给予依那普利口服治疗;治疗组在对照组基础上给予硝苯地平控释片口服治疗。观察2组临床疗效和血压改善情况。结果治疗组总有效率为95．0％高于对照组的81．7％,差异有统计学意义（P〈0．05）。治疗后2组血压均低于治疗前,且治疗组低于对照组,差异均有统计学意义（P〈0．05）。结论依那普利联合硝苯地平控释片治疗高血压病疗效显著,无明显不良反应,值得临床推广应用。     

硝苯地平控释片联合贝那普利治疗老年高血压疗效观察

目的观察硝苯地平控释片联合贝那普利治疗老年高血压临床疗效。方法老年高血压患者80例给予硝苯地平控释片及贝那普利口服治疗。治疗8周后比较治疗前后血压指标,评估其临床疗效。结果治疗4周后总有效率为73.75%,治疗8周后总有效率为85.00%。治疗4、8周后,血压下降情况与治疗前比较差异均有统计学意义(P<0.05或P<0.01)。80例患者发生刺激性干咳3例,头痛2例,踝关节水肿3例。结论硝苯地平控释片联合贝那普利治疗老年高血压疗效确切、安全性高、不良反应少,值得推广应用。     

Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients

Methadone, a synthetic racemic opioid that primarily works as a μ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients.     

CD1A and CD1E gene polymorphisms are associated with susceptibility to multiple sclerosis

Multiple sclerosis (MS) is thought to be an autoimmune T-cell-mediated disease directed at myelin antigens of the central nervous system. Besides myelin proteins, lipid components of CNS are supposed to play a role as antigens for T cells in MS. CD1 is a family of MHC-like glycoproteins specialized in capturing and presenting a variety of microbial and self lipids and glycolipids to antigen-specific T cells. CD1-restricted T cells specific for gangliosides and sulfatide have been isolated from subjects with MS and in mice with experimental allergic encephalopathy. We genotyped exon 2 of CD1A and CD1E in 205 MS patients and 223 unrelated healthy controls and determined their association with the presence of anti-ganglioside and anti-sulfatide antibodies. CD1E 01-01 is associated with a reduced risk of MS (OR 0.54, p=0.001); CD1A 02-02 (OR 1.99, p=0.012) or CD1E 02-02 (OR 2.45, p=0.000) with an increased risk. The combination of the genotypes CD1A 02-02 and CD1E 02-02 is present in 90.7% of patients but in only 9.4% controls (OR 94.16, p= 0.000). CD1A and CD1E polymorphisms contribute to the polygenic susceptibility to MS. The functional effects of CD1 polymorphisms are unknown, however changes in CD1 alleles may affect numerous immunological functions.