Objective To investigate the correlation between CYP2C19 gene polymorphisms and the incidence and prognosis of heart failure. Methods 1 368 patients who underwent parallel genomic testing and visited the Department of Cardiology at the People’s Hospital of Xinjiang Uygur Autonomous Region between June 2021 and December 2022 were selected. After quality control of genotype data, the patients were divided into a heart failure group and a control group based on diagnostic criteria. Genotyping of 31 genes and 62 single nucleotide polymorphism (SNPs) was performed using TaqMan-SNP genotyping technology. Differences in allele distribution and clinical indicators between the two groups were compared, and the incidence of cardiovascular adverse events in the heart failure group was followed up and calculated. Results A total of 1 352 patients were included. Among them, there were 169 cases in the heart failure group and 1 183 cases in the control group. At the rs12769205 locus of the CYP2C19 gene, the risk of disease for patients carrying the G allele was lower than those carrying the A allele (odds ratio=0.733, P=0.023). In addition to age, coronary heart disease, BMI, and the type of allele was also an independent influencing factor for heart failure (P＜0.05). Moreover, the level of cardiac troponin T in carriers of two mutant alleles was significantly higher than in carriers of one mutant allele (P =0.044) and in carriers of the wild-type allele (P=0.028). During the follow-up period, no significant differences were observed in the cumulative incidence of major cardiovascular adverse events among the three genotypes at the rs12769205 locus. Conclusion The polymorphic locus rs12769205 of the CYP2C19 gene is associated with the occurrence of heart failure, which may provide a theoretical basis for the diagnosis and treatment of heart failure.
ObjectiveTo explore the serum concentrations of complement C1q tumor necrosis factor related protein 5 (CTRP5) in patients with acute exacerbations and stable stage of chronic obstructive pulmonary disease (COPD), and analyze the correlation of CTRP5 with high sensitivity C-reactive protein (hs-CRP) and FEV1/FVC and FEV1%pred.MethodsThirty hospitalized patients with acute exacerbation of COPD and 30 outpatients with stable COPD according with diagnostic criteria and inclusive criteria were sampled successively. At the same time 30 healthy volunteers were selected as normal control. All subjects were measured the concentrations of CTRP5 and hs-CRP in serum and lung function test was performed.ResultsThe serum CTRP5 and hs-CRP concentrations of the acute exacerbation group was higher than those in the stable group and the control group. The serum CTRP5 and hs-CRP concentrations of the stable group was also higher than those of the control group. The FEV1/FVC of the acute exacerbation group was lower than those of the stable group and the control group; and the FEV1/FVC of the stable group was lower than that of the control group. The FEV1%pred of three groups by analysis indicated the difference was statistically significant. Further pairwise comparisons demonstrated that the FEV1%pred of two COPD groups were lower than that of the control group but the FEV1%pred of the acute exacerbation group and stable group was not significantly different. The correlation analysis of the acute exacerbation group and the stable group demonstrated that the levels of serum CTRP5 and hs-CRP were postively correlated and the level of serum CTRP5 was negatively correlated with FEV1/FVC and FEV1%pred.ConclusionsThe level of CTRP5 in serum of COPD patients is increased. No matter in acute exacerbation or stable phase, the level of serum CTRP5 is positively correlated with hs-CRP and negatively correlated with FEV1/FVC and FEV1%pred, which suggests that CTRP5 is involved in the pathogenesis of COPD but the exact mechanism needs further study.
Objective To explore the effects of mechanical stretch with variant frequencies on the alignment and differentiation of the multilayer myotubes cultured in vitro, and to select the optimized cultural condition of regenerative skeletal muscle tissue with stress loading cultured in vitro. Methods C2C12 myoblasts cultured in vitro in the groove casts of Sylgard 184 were induced into the multilayer myotubes. Meanwhile the myoblasts were treated with various mechanical stretch withcells tensile instrument, at the amplitude of 10% and the frequency of 0 (group A), 0.25 (group B), 0.50 (group C), and 1.00 Hz (group D) for 1 hour, 3 times a day. The myotubes morphology was observed by inverted phase contrast microscope at 5, 7, and 10 days after continuous mechanical stretch. And the expressions of mRNA for myogenic differentiation antigen (MyoD), Myogenin, Desmin, and myosin heavy chain (MyHC) were detected by RT-PCR and real-time fluorescent quantitative PCR (QRT-PCR), respectively. Results The mechanical stretch could promote the al igned fusion and increase the number of myotubes. Indeed the multilayer myotubes arranged more closely in group B at 7 days. At the same group, as the time went on, the mRNA expressions of MyoD gradually decl ined in each group. There were significant differences in mRNA expressions of MyoD between 5 days and 7, 10 days (P lt; 0.05). The mRNA expressions of Myogenin, Desmin, and MyHC were highest at 7 days. There were significant differences between different time points (P lt; 0.05), except the mRNA expression of Desmin of group B between 7 and 10 days (P gt; 0.05). At the same time, with the increase of frequency, the highest mRNA expressions of MyoD, Myogenin, Desmin, and MyHC were in group B. There were significant differences at the same time between group B and the other groups (P lt; 0.05), except mRNA expression of Desmin at 5 days between groups B and C, and mRNA expression of MyHC at 10 days between groups A and B (P gt; 0.05). Conclusion Low frequency (0.25 Hz) and suitable time (7 days) periodic mechanical stretch is beneficial to the differentiation of the multilayer myotubes cultured in the groove casts of Sylgard 184, but as the stretch time goes on the aging of myotubes will be accelerated.
Objective To analyze literatures reported allele frequencies of CYP2C191,2,3 for healthy Asian populations, and to provide evidence-based data for further personalized drug therapy and pharmacogenomics research. Methods Relevant articles were electronically retrieved from digital databases of PubMed, EMbase, The Cochran Library, CNKI, WanFang Data, VIP and CBM, and the articles reporting the allele frequencies of CYP2C19 were included. According to the inclusion and exclusion criteria, the data of the allele frequencies of the gene were extracted, pooled, and analyzed. Results A total of 41 articles were included, involving 9 841 healthy Asians from 17 countries. Analyses were conducted according to regional features, based on China, East Asia (China, Korea and Japan), Southeast Asia (Vietnam, Thailand, Malaysia, Singapore, Myanmar, Indonesia and Philippines), South Asia (India), and West Asia (Palestine, Lebanon, Saudi Arabia, Turkey, Iranian and Jordan). The major results showed that the allele frequencies of CYP2C191,2,3 were 61.3%, 32.1% and 6.6% (Chinese, n=4170); 61.0%, 31.2% and 7.8% (East Asians, n=5879); 67.6%, 28.8% and 3.7% (East South Asians, n=1985); 64.0%, 35.2% and 0.8% (South Asians, n=679); and 87.3%, 12.1% and 0.6% (West Asians, n=1298), respectively. Based on the included 9841 healthy Asians from 17 countries, the total allele frequencies of CYP2C191,2,3 were 66.0%, 28.4% and 5.5%, respectively. Conclusion The allele frequencies of CYP2C191,2,3 2 fairly differ in ethnic groups in China, as well as in regions in Asia. Besides, genetic variation is impacted by geographical factors such as regions and environment.
ObjectiveTo analyze genotype frequencies of CYP2C19 in healthy Asian population, and to provide evidence-based data for further personalized drug therapy and pharmacogenomics research. MethodsLiterature was retrieved from digital databases of PubMed, EMbase, The Cochrane Library (Issue 2, 2013), CNKI, WanFang Data, VIP and CBM from their established dates to August, 2013. According to the inclusion and exclusion criteria, the data of the allele frequencies of the gene were extracted, pooled, and analyzed. ResultsA total of 36 articles were included, involving 15 countries and 9 693 healthy populations. Analysis was conducted on regional features, by regions as China, East Asia (China, Korea and Japan), Southeast Asia (Vietnam, Thailand, Malaysia, Singapore, Myanmar and Indonesia), South Asia (India) and West Asia (Palestine, Lebanon, Iran, Turkey and Jordan). The results showed that the genotype frequencies of *1/*1, *1/*2, *1/*3, *2/*2, *2/*3 and *3/*3 were 37.2%, 41.4%, 6.7%, 9.9%, 4.1% and 0.7% (Chinese, n=4 105); 36.4%, 39.1%, 8.8%, 9.5%, 4.9% and 1.3% (East Asian, n=6 198); 44.9%, 41.1%, 4.7%, 7.0%, 1.8% and 0.6% (Southeast Asian, n=1 933); 43.5%, 42.9%, 0.3%, 12.7%, 0.6% and 0.0% (South Asian, n=361); 77.8%, 18.9%, 0.3%, 2.6%, 0.1% and 0.3% (West Asia, n=1 201); and 43.5%, 37.1%, 6.6%, 8.3%, 3.5% and 1.0% (Asian, n=9 693). ConclusionThe present study suggests that there is a great difference on the genotype frequencies of CYP2C19 for different ethnic groups in China, and at different regions in Asia. Besides, genetic variation is impacted by geographical factors such as region and environment.
ObjectiveTo evaluate anti-platelet effect of clopidogrel influenced by CYP2C19*17 polymorphism in patients with cardiovascular disease. MethodsWe electronically searched EMbase, PubMed, The Cochrane Library, ClinicalTrials.gov, CNKI, CBM, WanFang Data and VIP databases for cohort studies about the anti-platelet effect of clopidogrel influenced by CYP2C19*17 polymorphism in patients with cardiovascular disease from inception to October 2012. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using the software Rev-Man 5.2. ResultsA total of seven studies involving 12 116 patients were finally included. Three were 5 579 CYP2C19*17 carriers and 6 538 non-carriers. The results of meta-analyses showed that, compared with the CYP2C19*17 non-carriers, lower rate of cardiovascular events (OR=0.85, 95%CI 0.73 to 0.99, P=0.03) and higher bleeding events (OR=1.25, 95%CI 1.05 to 1.50, P=0.01) were found in the CYP2C19*17 carriers. ConclusionCYP2C19*17 carriers is with lower cardiovascular events and higher bleeding events than the CYP2C19*17 non-carriers.
Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.
Objective To investigate the influence of CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms on warfarin dosages of patients after heart valve replacement. Methods A total of 133 patients undergoing heart valve replacement in the Department of Cardiovascular Surgery of Fujian Provincial Hospital from November 2011 to August 2012 were included in this study. Polymerase chain reaction（PCR）gene sequencing was performed to detect CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphism of these 133 patients. Patients were grouped according to their genotypes，and average warfarin dosages were compared between different genotype groups. Results The frequencies of CYP2C9 3 AA，AC and CC were 127 patients，6 patients and 0 patient respectively，and average daily warfarin dosages were 3.75 mg and 2.13 mg respectively which were statistically different between differentCYP2C9 3 genotypes （P＜0.05）. The frequencies of VKORC1-1639 G＞A GG，GA and AA were 3 patients，32 patientsand 98 patients respectively，and average daily warfarin dosages were 6.00 mg，4.50 mg and 3.00 mg respectively which were statistically different between different VKORC1-1639 G＞A genotypes （P＜0.05）. The frequencies of CYP4F2 rs 2108622 CC，CT and TT were 67 patients，59 patients and 7 patients respectively，and average daily warfarin dosages were 3.00 mg，3.75 mg and 4.50 mg respectively which were statistically different between different CYP4F2 rs2108622 genotypes（P＜0.05）. Conclusion CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms are associated with individual difference of warfarin dosages of patients after heart valve replacement.
Gitelman syndrome (GS) is an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. The disorder is named for Gitelman, an American nephrologist. He first described it in 1966, after observing a pair of sisters with the disorder. The disorder is caused by inactivating mutations in the SLC12A3 gene, resulting in improper function of the thiazide-sensitive sodium-chloride co-transporter located in the distal convoluted tubule of the kidney. GS was formerly considered a subset of Bartter syndrome until the distinct genetic and molecular bases of these disorders were identified. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. This review aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been strongly associated with warfarin maintenance doses. Warfarin maintenance doses can be accurately predicted by use of dosing algorithms including genetic and clinical information. Although several clinical trials demonstrated mixed results, calling into question the utility of this approach. The present data do not support genetic testing to guide warfarin maintenance doses, but in the setting where genotype data are available, use of this approach is reasonable. Ongoing trials are expected to provide more data, and more work is needed to define dosing algorithms that include appropriate variables in minority populations. All these work will further improve the clinical application of genotype-guided warfarin maintenance doses.