Effects of gene polymorphism on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin treatment in stage Ⅲ and Ⅳ colorectal cancer / 中国药房

OBJECTIVE To investigate the effects of GSTP1， XRCC1， ABCB1， MTHFR gene polymorphisms on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin in patients with stage Ⅲ and Ⅳ colorectal cancer patients. METHODS Clinical data of 76 patients with stage Ⅲ and Ⅳ colorectal cancer who received chemotherapy regimen containing oxaliplatin （XELOX，FOLFOX） were collected from the Second Affiliated Hospital of Soochow University from September 2018 to March 2020. The correlation of genotypes with progression-free survival （PFS） and toxic effect was analyzed by using univariate and multivariate COX regression model. RESULTS Carriers of the ABCB1 3435T＞C locus C allele （TC/CC） had a significantly higher risk of progression compared to TT genotype patients [HR＝2.39， 95%CI （1.05，5.50）， P＝0.038]. The risk of progression in patients at stage Ⅳ was significantly higher than those at stage Ⅲ [HR＝8.11， 95%CI（3.39，19.40）， P＜0.001]. Chemotherapy regimen， Karnofsky performance status score and tumor site had no significant effect on disease progression （P＞0.05）. Mutations in gene loci were not correlated with adverse reactions （P＞0.05）. CONCLUSIONS Patients carrying ABCB1 TC/CC and receiving chemotherapy regimen containing oxaliplatin have a higher risk of disease progression， which may be associated with longer PFS in patients （TT genotype） with stage Ⅳ colorectal cancer receiving the chemotherapy， while GSTP1， XRCC1， and MTHFR gene polymorphisms have no significant impact.

Meta-analysis about ADRB1 Arg389Gly polymorphism on the efficacy of bisoprolol / 中国药房

OBJECTIVE To explore the effects of ADRB1 Arg389Gly polymorphisms on the efficacy of bisoprolol， thus providing some information for individualized drug therapy. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CBM， CNKI， and Wanfang Data to retrieve and find out all relevant literature about bisoprolol and ADRB1 Arg389Gly polymorphism from the inception to May 2023. The retrieved literature was screened and selected according to the inclusive and exclusive criteria， thereafter quality assessment was conducted. RevMan 5.4 software was utilized to perform the meta- analysis for the outcome index. RESULTS Overall 7 literature with 1 339 cases were included. Among them， 4 studies provided the changes in systolic blood pressure （SBP）， diastolic blood pressure （DBP） （ΔSBP and ΔDBP）； 4 involving the change （ΔLVEF） of left ventricular ejection fraction （LVEF）. Results of the study showed that there was no statistical significance in the improvement of blood pressure between wild-type group （AA） and mutation group （AG+GG） of ADRB1 Arg389Gly treated with bisoprolol {ΔSBP [SMD＝0.17，95%CI （－0.97，1.31）， P＝0.77]， ΔDBP [SMD＝－0.01，95%CI （－0.65，0.62）， P＝0.97]}； there was no statistical significance in the improvement of ΔLVEF [SMD＝－0.61， 95%CI （－2.74，1.53）， P＝0.58] between 2 groups. CONCLUSIONS ADRB1 Arg389Gly gene polymorphism has no significant influence on the improvement of SBP， DBP， and LVEF in cardiovascular patients who use bisoprolol.

miR604A>G gene polymorphism is associated with recurrent pregnancy loss in Turkish women

SUMMARY OBJECTIVE: Recurrent pregnancy loss is considerably a reproductive health problem for couples. Genetic, epigenetic, and environmental factors play an important role in the development of recurrent pregnancy loss. While there are many causes, genetic and epigenetic factors are common. In this study, we aimed to examine the association between miR604 (rs2368393) A>G gene polymorphism and the risk of recurrent miscarriage in the Turkish population. METHODS: The study included 250 participants (i.e., 150 patients and 100 controls). DNA samples were isolated from peripheral blood, and polymerase chain reactions and restriction fragment length polymorphism methodologies were applied. RESULTS: The genotype distribution and allele frequencies of miR604A>G gene showed statistically significant differences between patients and control groups (p=0.002 and p<0.002, respectively). CONCLUSION: As a result of the study, we found that the AA genotype and A allele of the miR604A>G gene were statistically significant for the risk of recurrent pregnancy loss in Turkish women.

The relationship between MMP-2 rs243865, MMP-9 rs398242 and CXCL-12 rs1801157 gene polymorphisms with Japanese encephalitis disease and disease outcome in North Indian population

Background & objectives: Japanese encephalitis virus (JEV) is one of the most important causes of acute and uncontrolled inflammatory disease in Asia. Matrix metalloproteinases (MMPs) and chemokines play a detrimental role in the host response to JE disease, aetiology, and disease outcome. Evidently, MMPs are widely circulated in the brain and regulate various process including microglial activation, inflammation, blood-brain barrier disruption as well as affects central nervous system (CNS). The present study was to assess the association of single nucleotide polymorphisms of MMP-2, MMP-9 and chemokine (CXCL-12/SDF1-3’) in the north Indian population. Methods: We performed case-control study comprising of 125 patients and 125 healthy controls in north Indian population. Genomic DNA was extracted from whole blood and gene polymorphism have been determined by PCR-RFLP method. Results: MMP-2, MMP-9 and CXCL-12 gene was not significantly associated with JE disease, but homozygous (T/T) genotype of MMP-2 was statically associated with disease outcome (p=0.05, OR=0.110). A/G and G/G genotype of CXCL-12 was significantly associated with severity of disease. (p=0.032, OR=5.500, p=0.037, OR= 9.167). The serum level of MMP-2 was observed significantly increased in JE patients with homozygous (T/T) genotype whereas increased MMP-9 level was associated with heterozygous genotype. Interpretation & conclusion: MMP-2, MMP-9 and CXCL-12 gene polymorphism were not associated with JE susceptibility, but MMP-2 may be contributed to disease protection. CXCL-12 was associated with disease severity. In our concern this is the first report from northern India.

Relationship between ALDH2 rs671 gene polymorphism and body fat content in Han population / 中华健康管理学杂志

Objective:To investigate the relationship between ALDH2 rs671 gene polymorphism and body fat content in Chinese Han population.Methods:It was a cross-sectional study. A total of 3 943 Chinese Han people were selected for physical examination in the Department of Health Medicine in the Second Medical Center of Chinese PLA General Hospital from January 2017 to January 2020, including 2 749 males and 1 194 females; the average age was (48.12±7.98) years. The research subjects were divided into obesity group and non-obesity group according to their body fat rate. The basic information including age, gender, disease history, height, weight, body fat content and blood samples were collected; the ALDH2 rs671 gene polymorphism was detected. Genotype and allele frequencies were compared between groups by using χ2 test. The comparison of clinical data between different genotypes was conducted by using one-way analysis of variance. The correlation between various indicators, lifestyle and genotype was analyzed by using a logistic regression model. Results:The distribution of ALDH2 rs671 genotype was wild genotype GG (68.6%), heterozygous mutant genotype GL (28.7%) and homozygous mutant genotype LL (2.7%). In terms of baseline characteristics, there were significant differences in male (67.5% vs 71.3%), body mass index (BMI, (23.12±2.64) kg/m 2 vs (27.10±2.75) kg/m 2), genotype distribution (GG 65.6% vs 70.6%), drinking history (64.4% vs 68.8%), history of hypertension (18.7% vs 36.9%), coronary heart disease (3.7% vs 5.6%) and diabetes (9.7% vs 15.0%) between the obesity and non-obesity group (all P<0.05). Multifactor logistic regression showed that ALDH2-GG genotype ( OR=1.386, 95% CI: 1.078-1.782), age ( OR=1.051, 95% CI: 1.035-1.068), and BMI ( OR=2.182, 95% CI: 2.043-2.331) were risk factors for obesity differentiated by body fat percentage, and male ( OR=0.175, 95% CI: 0.123-0.250) was protective factor (all, P<0.05). Conclusion:ALDH2 rs671 polymorphism is related to body fat content. The risk of excessive body fat content in individuals with GG genotype is significantly increased.

Lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different genotypes of ATP-binding cassette subfamily B member 1 G2677T / 中华行为医学与脑科学杂志

Objective:To observe the lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different ATP-binding cassette subfamily B member 1(ABCB1) genotypes, and thus to provide clinical research evidence for individual application of atorvastatin in patients with acute cerebral infarction.Methods:From March 2021 to December 2021, 131 patients with acute cerebral infarction admitted to the Department of Neurology of Xuchang Central Hospital were included. The ABCB1 G2677T gene polymorphism rs2032582 of patients was detected by fluorescence staining in situ hybridization.Based on the detection results, patients were divided into GG group, GT group and TT group.All patients were given atorvastatin (20 mg/d) for lipid-lowering treatment.The levels of low density lipoprotein cholesterol(HDL-C), high density lipoprotein cholesterol(HDL-C), total cholesterol(TC)and triglyceride(TG) in serum of patients in the three groups before and 2 months after treatment were recorded and analyzed.The adverse drug reactions in the three groups were recorded. When the serum LDL-C level was less than 1.8 mmol/L, it was considered that the lipid-lowering treatment was effective.The binary Logistic regression analysis was used to explore the influencing factors of atorvastatin lipid lowering therapy.The software of SPSS 25.0 was used for statistical analysis.Results:There were 50 (38.17%), 49 (37.40%) and 32 (24.43%) patients in GG group, GT group and TT group, respectively. The serum TC levels of patients in GG group, GT group and TT group after treatment were (3.47±0.70) mmol/L, (3.59±1.09) mmol/L and (3.48±1.02) mmol/L, respectively, which were lower than those before treatment ((4.27± 0.99) mmol/L, (4.02±0.98) mmol/L and (4.03±1.31) mmol/L), all of which were statistically significant ( t=7.652, 3.092, 5.593, all P<0.01). The serum LDL-C levels in GG group, GT group and TT group after treatment were (1.89±0.53) mmol/L, (2.07±0.92) mmol/L and (1.96±0.79) mmol/L, respectively, which were lower than those before treatment ((2.87±0.92) mmol/L, (2.56±0.89) mmol/L and (2.55±1.11) mmol/L) ( t=9.896, 4.055, 5.980, all P<0.001). The differences of serum LDL-C level before and after treatment in GG group, GT group and TT group were (-0.97±0.69) mmol/L, (-0.50±0.86) mmol/L and (-0.59±0.56) mmol/L, respectively. The difference of serum LDL-C level before and after treatment in the three groups was statistically significant ( F=5.614, P=0.005). The difference of TC, TG and HDL-C before and after treatment was not statistically significant( F=2.783, 0.490, 1.677, all P>0.05). The binary Logistic regression analysis showed that ABCB1 G2677T gene type and staying up late were independent influencing factors for atorvastatin lipid-lowering therapy. The probability of effective lipid-lowering in GT patients with ABCB1 G2677T gene was 27.9% of that in GG patients ( OR=0.279, 95% CI: 0.110-0.709, P=0.007), and the probability of TT type patients was 33.8% of GG type patients ( OR=0.338, 95% CI: 0.121-0.943, P=0.038). The probability of effective lipid-lowering in patients who had the habit of staying up late was 26.4% of the patients who did not stay up late ( OR=0.264, 95% CI: 0.118-0.591, P=0.001). There was no significant difference in the total incidence of adverse drug reactions among the three groups( χ2=0.868, P=0.648). Conclusion:The lipid-lowering effect in patients with GG type of ABCB1 G2677T is better than that of GT type and TT type when atorvastatin is used to treat patients with acute cerebral infarction.

Molecular characteristics of clinically isolated Yersinia in Jiangsu Province from 2017 to 2021 / 中华地方病学杂志

Objective:To investigate the distribution and molecular characteristics of Yersinia isolated from diarrhea patients in Jiangsu Province. Methods:From 2017 to 2021, the stool samples of diarrhea patients were collected in Tongshan District of Xuzhou City and Dongtai City of Yancheng City, Jiangsu Province, where the national active monitoring sites of Yersinia enterocolitica, then Yersinia was isolated; meanwhile, suspected Yersinia strains were collected from sentinel hospitals in the province. The DNA of isolated strains was extracted for whole genome resequencing, and the data were uploaded to the EnteroBase database for Yersinia species identification; the original data were cleaned and processed for 16S ribosomal RNA (16S rRNA) gene polymorphism analysis. Five virulence genes (ail, ystA, ystB, yadA, virF) were scanned through the National Center for Biotechnology Information (NCBI) and Pathogen Virulence Factor Database (VFDB), and K-mer Tree was constructed and genomic characteristics were analyzed. Results:From 2017 to 2021, a total of 2 058 stool samples from diarrhea patients were collected, and 57 strains of Yersinia were isolated and identified; meanwhile, two Yersinia strains were collected from the sentinel hospital. Compared with EnteroBase database, 51 strains were identified as Yersinia enterocolitica, 4 strains as Yersinia proxima, 1 strain each as Yersinia aleksiciae, Yersinia massiliensis, Yersinia intermedia and Yersinia canariae. The 16S rRNA gene polymorphism analysis showed that all strains were clustered into 3 groups, which could distinguish Yersinia enterocolitica from other Yersinia. Among the 51 strains of Yersinia enterocolitica, 49 strains were virulence genotype Ⅲ(ail-, ystA-, ystB+, yadA-, virF-), two strains were virulence genotype Ⅱ(ail+, ystA+, ystB-, yadA-, virF-); and 8 other Yersinia strains were virulence genotype Ⅳ (ail-, ystA-, ystB-, yadA-, virF-). K-mer analysis could distinguish Yersinia enterocolitica from other Yersinia, JS-XZ-2020001 strain was far away from other Yersinia enterocolitica isolates, and serotype O8 strains were more concentrated. Conclusions:The clinical isolates of Yersinia enterocolitica from diarrhea patients are mainly Yersinia and other Yersinia co-exist in a small amount in Jiangsu Province, two new Yersinia species ( Yersinia proxima and Yersinia canariae) are discovered. The virulence genotype of Yersinia enterocolitica is mainly type Ⅲ. The 16S rRNA gene polymorphism analysis and K-mer analysis can effectively distinguish Yersinia enterocolitica from other Yersinia.

The evaluation value of cytochrome P450 2C19 *2 gene polymorphism, Helicobacter pylori infection for clopidogrel effect in patients with coronary heart disease / 中国医师进修杂志

Objective:To explore the evaluation of cytochrome P450 2C19 *2 (CYP2C19 *2) gene polymorphism and Helicobacter pylori (Hp) infection for clopidogrel efficacy in patients with coronary heart disease. Methods:The clinical data of 113 patients with coronary heart disease from February 2016 to March 2020 in Suzhou High-tech Zone People′s Hospital were retrospectively analyzed. The CYP2C19 *2 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, the Hp infection was detected by 13C urea breath test. The patients were treated with clopidogrel, the effect after 4 weeks was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the CYP2C19 *2 gene polymorphism and Hp infection for evaluating clopidogrel effect in patients with coronary heart disease. Results:The CYP2C19 *2 genotype in patients with coronary heart disease conformed to Hardy-Weinberg balance ( χ2 = 0.33, P>0.05). Among 113 patients with coronary heart disease, Hp infection was in 27 cases, and Hp non-infection in 86 cases. Among Hp infection patients, CYP2C19 *2 gene GG was in 2 cases, GA in 6 cases, AA in 19 cases; among Hp non-infection patients, CYP2C19 *2 gene GG was in 23 cases, GA in 46 cases, AA in 17 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two ( χ2 = 24.35, P<0.01). After clopidogrel treatment, effectiveness was in 79 cases, inefficiency in 34 cases. Among effectiveness patients, YP2C19 *2 gene GG was in 20 cases, GA in 43 cases, AA in 16 cases; among inefficiency patients, CYP2C19 *2 gene GG was in 5 cases, GA in 9 cases, AA in 20 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two groups ( χ2 = 16.35, P<0.01). The rate of Hp infection in effectiveness patients was significantly lower than that in inefficiency patients: 12.66% (10/79) vs. 50.00% (17/34), and there was statistical difference ( χ2 = 18.23, P<0.05). ROC curve analysis result showed that the area under the curve of CYP2C19 *2 gene polymorphism combined with Hp infection for evaluating clopidogrel effect in patients with coronary heart disease was larger than CYP2C19 *2 gent GG, GA, AA and Hp infection alone evaluating (0.973 vs. 0.869, 0.679, 0.884 and 0.728) . Conclusions:The CYP2C19 *2 gene polymorphism is associated with Hp infection in patients with coronary heart disease, and the CYP2C19 *2 gene polymorphism combined with Hp infection has the evaluation value for the efficacy of clopidogrel.

Association of UGT1A1 gene G71R polymorphism with neonatal hyperbilirubinemia / 中国小儿急救医学

Objective:To explore the association between the G71R polymorphism of the UGT1A1 gene and neonatal hyperbilirubinemia. Methods:DNA was extracted from blood samples of 61 neonates with severe neonatal hyperbilirubinemia(severe neonatal hyperbilirubinemia group), 60 neonates with hyperbilirubinemia(hyperbilirubinemia group) and 62 healthy neonates(control group), the G71R mutation of UGT1A1 gene was analyzed by direct sequencing. Results:In severe neonatal hyperbilirubinemia group, there were 17 cases of homozygous mutation(A/A), 23 cases of heterozygous mutation(A/G) , and 21 cases of wild type(G/G) , with 28.87% homozygous mutation rate and 37.70% heterozygous mutation rate.In neonatal hyperbilirubinemia group, there were ten cases of homozygous mutation(A/A), 28 cases of heterozygous mutation(A/G) and 22 cases of wild type(G/G), with 16.67% homozygous mutation rate and 46.67% heterozygous mutation rate.In the control group, there were nine cases of homozygous mutation (A/A), 28 cases of heterozygous mutation(A/G) and 25 cases of wild type(G/G), among which the homozygous mutation rate was 14.52% and the heterozygous mutation rate was 45.16%.The genotype frequency( χ2=4.14, P=0.38)and allele frequency( χ2=2.47, P=0.29)of G71R in severe neonatal hyperbilirubinemia group, neonatal hyperbilirubinemia group and control group were not statistically significant. Conclusion:The G71R polymorphism of the UGT1A1 gene may not be significantly correlated with the prevalence of neonatal hyperbilirubinemia.

AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis / 南方医科大学学报

OBJECTIVE@#To explore the correlation of polymorphisms of AF4/FMR2 family genes and IL-10 gene with genetic susceptibility to ankylosing spondylitis (AS) and identify the high-risk factors of AS.@*METHODS@#This case-control study was conducted among 207 AS patients and 321 healthy individuals. The tag single nucleotide polymorphisms (SNPs) rs340630, rs241084, rs10865035, rs1698105, and rs1800896 of the AF4/FMR2 family gene and IL-10 gene of the AS patients were genotyped, and the distribution frequencies of the genotypes and alleles were analyzed to explore the relationship between different genetic models and AS and the gene-gene and gene-environment interactions.@*RESULTS@#Gender ratio, smoking history, drinking history, hypertension, erythrocyte sedimentation rate and C-reactive protein differed significantly between the case group and the control group (P < 0.05). The dominant model and recessive model of AFF1 rs340630, the recessive model of AFF3 rs10865035, and the recessive model of IL-10 rs1800896 were significantly different between the two groups (P=0.031, 0.010, 0.031, and 0.019, respectively). Gene-environment interaction analysis suggested that the interaction model incorporating AFF1 rs340630, AFF2 rs241084, AFF3 rs10865035, AFF4 rs1698105, IL-10 rs1800896, smoking history and drinking history was the best model. The genes related with AF4/FMR2 and IL-10 were enriched in the biological processes of AF4 super extension complex, interleukin family signal transduction, cytokine stimulation and apoptosis. The expression levels of AF4/FMR2 and IL-10 were positively correlated with immune infiltration (r > 0).@*CONCLUSION@#The SNPs of AF4/FMR2 and IL-10 genes are associated with the susceptibility to AS, and the interactions of AF4/FMR2 and IL-10 genes with the environmental factors contributes causes AS through immune infiltration.

Relationship between ANKK1 gene polymorphism and atypical antipsychotic drug-induced metabolic syndrome / 中国药房

OBJECTIVE To explore the relationship between the ANKK1 rs1800497 polymorphism and atypical antipsychotic drug-induced metabolic syndrome （MS）. METHODS Totally 94 patients with schizophrenia were included， and ANKK1 rs1800497 genotypes of patients were detected by micro-fluorescence immunoassay； social demographic information， clinical characteristics and other data were collected. The χ2 test was used to compare the correlation between the sex of patients and the occurrence of MS， and the correlation between gene polymorphism and the occurrence of MS and its risk factors.RESULTS Totally 94 patients included 24 cases （25.53%） of GG， 51 cases （54.26%） of GA and 19 cases of AA （20.21%）. Among them， there were 45 cases （47.87%） of MS， and the incidence of MS in male was higher than that in female （P＜0.05）. Genotype analysis showed that ANKK1 rs1800497 polymorphism was not associated with MS （P＝0.452）. ANKK1 rs1800497 A allele was significantly associated with hyperglycemia （χ2＝4.379， P＝0.036）， while it was not related to abdominal obesity， hypertension， high level of TG and low level of HDL-C （P＞0.05）， suggesting that for patients with schizophrenia， allele A was a relative risk factor for inducing hyperglycemia [OR＝2.008，95%CI（1.039， 3.881）]. CONCLUSIONS ANKK1 rs1800497 polymorphism has no correlation with the induction of MS by atypical antipsychotics， while the schizophrenia patients with A allele are more likely to induce hyperglycemia. The incidence of MS in male patients is significantly higher than that in female patients.

Clinical study of TBX21 and ADCY9 polymorphisms in the development of childhood asthma / 中国临床药理学与治疗学

To investigate the clinical role of T-cell transcription factor (TBX21) and adenylate cyclase 9 antibody (ADCY9) gene polymorphisms in the development of childhood asthma. METHODS: Two hundred Han Chinese wheezing children aged 5 years and younger in Henan region from July 2016 to January 2017 were selected as the study group, and another 100 Han Chinese healthy children aged 5 years and younger in the same period were selected as the control group. Oral mucosal exfoliated cells were collected from both groups, and the genotypes of TBX21 gene rs2240017 polymorphic locus and ADCY9 gene rs2230739 polymorphic locus were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) technique, and the risk level of asthma was assessed based on the test results. The children in the low-risk and high-risk groups were compared in terms of serum immunoglobulin E (IgE) levels, API positivity rate and allergic disease incidence, and the correlation between the risk level of asthma-related genetic polymorphisms and serum IgE levels, API and allergic disease incidence was analyzed. All children were followed up until 6 years of age to confirm the diagnosis of asthma, and the incidence of asthma was compared between the low-risk and high-risk groups. Children with asthma were treated with inhaled glucocorticoids and leukotriene receptor antagonists for 3 months, and the control of asthma and the impairment of lung function were compared between the low-risk and high-risk groups. RESULTS: The genotype detection results of rs2240017 polymorphic locus of TBX21 gene and rs2230739 polymorphic locus of ADCY9 gene in the study group compared with those in the control group were statistically significant (P<0.001). The percentages of CC, CT, and TT genotypes of rs2240017 polymorphic locus of TBX21 gene were 19.50%, 56.00%, and 24.50%, respectively, and the percentages of CC, CG, and GG genotypes of rs2230739 polymorphic locus of ADCY9 gene were 86.00%, 10.00%, and 4.00%, respectively, in 200 children with wheezing; serum IgE level, API positivity rate and allergic disease incidence were higher in the high-risk group than in the low-risk group (P< 0.001, <0.001, 0.021, respectively). The degree of risk of asthma-related gene polymorphisms in children with wheezing was positively correlated with serum IgE levels, API positivity, and the incidence of allergic diseases (P<0.001); the incidence of asthma (81.48%) and impaired lung function (74.07%) were higher in the high-risk group than in the low-risk group (4.90%, 3.50%) (P<0.001). There was no statistically significant difference between the asthma control rate of children with asthma in the high-risk group (79.55%) compared with the asthma control rate of children with asthma in the low-risk group (100.00%) (P=0.433). CONCLUSION: Gene polymorphisms at rs2240017 locus of TBX21 gene and rs2230739 locus of ADCY9 gene are closely associated with asthma development and impaired lung function in children with wheezing.

Effects of single nucleotide polymorphism of drug metabolizing enzyme cytochrome P450 on the efficacy of inhaled cortisol hormone in asthmatic children / 中国临床药理学与治疗学

AIM: To elucidate the relationship between childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids (ICS) in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymorphisms (SNPs) of cytochrome P450 enzyme 3A5 (CYP3A5) gene in asthmatic children and healthy children. METHODS: The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 children (Case group) with asthma of Han nationality and 100 healthy children (Control group) who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020, and genotype, allele and linkage analysis were performed. The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months, and lung function and exhaled breath nitric oxide (FeNO) were measured at entry and after treatment, and asthma control score C-ACT/ACT was done after treatment, so as to compare the prevalence of different genotypes and the differences in the above test index scores. RESULTS: There was complete linkage disequilibrium at rs776746 and rs15524 loci. There were three genotypes of T/T, T/C and C/C at rs776746 locus of CYP3A5 gene. There were significant differences in the frequency of different genotypes between the case group and the control group (χ

The correlation between FCER2 gene polymorphism and the efficacy of inhaled corticosteroids in patients with chronic rhinosinusitis / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the correlation between FCER2（2206A>G） gene polymorphism and the efficacy of inhaled corticosteroids（ICS） in patients with chronic rhinosinusitis（CRS）. Methods:A total of 208 CRS patients were routinely treated with functional endonasal sinus surgery and postoperative ICS. DNA extraction, PCR amplification and gene sequencing were performed to observe the FCER2（2206A>G） gene polymorphism and calculate the allele frequency. The visual analog scale（VAS） score, Lund-Kennedy score, and computed tomography（CT） Lund-Mackay score were determined 6 months after surgery among patients with different genotypes. Moreover, the polymorphism frequency was compared among different subgroups（chronic rhinosinusitis with nasal polyps versus chronic rhinosinusitis without nasal polyps, eosinophilic chronic rhinosinusitis versus non-eosinophilic chronic rhinosinusitis）. Results:There were FCER2（2206A>G） gene polymorphism in patients with CRS, and the phenotypes included 3 genotypes, AA, AG and GG, with distribution frequencies of 68（32.7%）, 116（55.8%） and 24（11.5%） cases, respectively. No significant differences were found in age, VAS score, nasal endoscopic Lund-Kennedy score and CT imaging Lund-Mackay score among patients with CRS of each genotype before surgery. In patients with the AA genotype, the changes in VAS score（5.74±1.10）, Lund Kennedy score（5.92 ± 1.14）, and CT imaging Lund-Mackay score（13.26±4.26） were significantly higher than in patients with the AG（4.37±0.86, 5.37±1.24, 10.82±3.77） and GG（4.26±0.80, 5.18±1.56, 10.10±3.53） genotype（P<0.05）. However, there were no marked difference between patients with the AG genotype and those with the GG genotype（P>0.05）. Compared with patients with non-eosinophilic sinusitis, Among them, the differences between the GG genotype and AG /AA genes were more significant in eosinophilic sinusitis compared to non-eosinophilic sinusitis（P<0.01）. Conclusion:The FCER2（2206A>G） gene in patients with CRS has genetic polymorphism and is associated with the recovery of CRS patients after surgery, individual corticosteroid sensitivity, and subgroup variability.

Association of Toll-like receptor 7, CTLA-4 gene polymorphisms with severe asthma / 公共卫生与预防医学

Objective To explore the association of Toll-like receptor 7, CTLA-4 gene polymorphisms and severe asthma. Methods From February 2018 to March 2020, 175 asthma patients admitted to the respiratory department of our hospital were selected as the research subjects (109 cases of mild disease and 66 cases of severe disease), and 248 cases of healthy people who were included in the outpatient physical examination of our hospital during the same period were selected as the normal control group. Toll-like receptor 7 and CTLA-4 gene polymorphisms in the above groups were determined, and the relationship between Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma was evaluated by calculating the odds ratio (OR) and 95% confidence interval(CI). The relationship between the genotypes of Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma were evaluated by logistic regression analysis. Results The proportion of TLR7 rs3853839 CC genotype, CTLA-4 rs231725 AA genotype, TLR7 rs3853839 C allele frequency and CTLA-4 rs231725 A allele frequency in severe asthma group and mild asthma group were higher than those in normal control group(P<0.05). The proportion of TLR7 rs3853839 CC genotype, the proportion of CTLA-4 rs231725 AA genotype, the frequency of TLR7 rs3853839 C allele, and the frequency of CTLA-4 rs231725 A allele in the severe asthma group were higher than those in the mild asthma group(P<0.05). TLR7 rs3853839 CC genotype (OR=10.32, 95%CI=5.59-23.89), CTLA-4 rs231725 AA genotype (OR=13.21, 95%CI=3.58-20.25), TLR7 rs3853839 C allele frequency (OR=11.32, 95% CI=4.25-21.14) and CTLA-4 rs231725 A allele frequency (OR=13.24, 95% CI=6.59-20.21) could increase the susceptibility to severe asthma(P<0.05). TLR7 rs3853839CC genotype, TLR7 rs3853839C allele frequency, CTLA-4 rs231725AA genotype and CTLA-4 rs231725A allele frequency were risk factors for severe asthma(P<0.05). Conclusion TLR7 rs3853839 CC genotype, TLR7 rs3853839 C allele frequency, CTLA-4 rs231725 AA genotype and CTLA-4 rs231725 A allele frequency are associated with the occurrence of severe asthma.

Distribution of gene mutation sites affecting artemisinin metabolism in the Kazak population in Xinjiang / 中国热带医学

@#Abstract: Objective　To detect the distribution of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 loci affecting the metabolism of artemisinins in Kazak population in Xinjiang. To explore the pharmacogenetic background of the Kazak population in Xinjiang for artemisinin drugs and provide clinical decision support for the treatment and prevention of malaria based on artemisinin drugs. Methods　Six SNPs including CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 were selected for the sequencing experiment. 330 whole blood samples were collected from the Kazak population in Xinjiang. After extracting the whole blood DNA genome, multiplex PCR and high-throughput sequencing were used for genotyping. The allele frequencies were analyzed using the Hardy-Weinberg equilibrium. Results　In this study all SNPs follow the Hardy-Weinberg equilibrium (P>0.05), there was no significant difference in the distribution of SNPs between different genders (P>0.05). The number of successfully sequenced samples of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 were 326, 319, 328, 318, 322 and 328 respectively. The frequencies of variant alleles of CYP2A6∗2, CYP2A6∗10, CYP2A6∗17, CYP2B6∗4, CYP2B6∗6, and CYP2B6∗18 in Kazak population are: 0.61%, 0%, 0%, 30.97%, 22.98%, 0%. Conclusions　Mutation alleles affecting the metabolism of artemisinins exist in the Kazak population in Xinjiang. When using artemisinins, the relationship between the drug effect and individual pharmacogenetic background should be further explored.

Application of gene detection in individualized treatment of lipid-lowering drugs / 中国药房

The main clinical manifestation of dyslipidemia is hyperlipidemia， which is an important risk factor leading to the occurrence of cardiovascular and cerebrovascular diseases such as atherosclerosis， coronary heart disease and stroke. In clinical practice， lipid-lowering drugs are mainly used for treatment， but there are issues such as individual differences and genetic effects. Therefore， it is necessary to perform gene detection on patients， so as to guide individualized application of lipid-lowering drugs. This review mainly previews the definition of gene detection and the individualized treatment of lipid-lowering drugs， and introduces the application of gene detection in the individualized treatment of lipid-lowering drugs （statins， fibrates， nicotinic acid and ezetimibe）. Among them， the gene polymorphisms of APOE， SLCO1B1 and CYP450 family play a key role in the efficacy and safety of statins； the gene polymorphisms of APOA/B/C family have a significant impact on the efficacy of fenofibrate； the gene polymorphisms of HCAR2 and DGAT2 have an important impact on the efficacy of niacin； the gene polymorphisms of NPC1L1 have a significant impact on the efficacy of ezetimibe. It is suggested to conduct genotype detection for patients with dyslipidemia to select appropriate treatment strategies， so as to provide individualized medication guidance.

Study on the correlation between opioid-induced constipation and gene polymorphism / 中国药房

OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.

Gene Polymorphisms of Patients with Lymphoma-Associated Hemophagocytic Syndrome in Longyan area, Fujian Province / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province.@*METHODS@#A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed.@*RESULTS@#The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively.@*CONCLUSION@#PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.

Recent research on the association between depressive disorder and gene polymorphisms in adolescents / 中国当代儿科杂志

Biogenetics plays an important role in the pathogenesis of depressive disorder in adolescents. Various genetic polymorphism studies have updated the understanding of adolescent depressive disorder. However, due to the influence of gene-environment interaction and age of puberty, the influence of gene polymorphisms on adolescent depressive disorder is complicated to clarify. Investigating and clarifying the relationship between gene polymorphisms and adolescent depressive disorder will promote the research on the pathogenesis of this disorder and provide a reference for the prevention and treatment of this disorder. This article reviews the genetic polymorphisms related to adolescent depressive disorder.