Genetic polymorphisms in hMTH1, hOGG1 and hMYH and risk of chronic benzene poisoning in a Chinese occupational population

Oxidative damage to DNA induced by benzene is an important mechanism of its genotoxicity, which leads to chronic benzene poisoning (CBP). Therefore, genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population. We hypothesized that single nucleotide polymorphisms (SNPs) in hMTH1, hOGG1 and hMYH genes are associated with risk of CBP. We genotyped SNPs at codon 83 of hMTH1, codon 326 of hOGG1, and codon 324 of hMYH in 152 CBP patients and 152 healthy workers occupationally exposed to benzene without poisoning manifestations. The genotypes were determined by polymerase chain reaction-restrained fragment length polymorphism (PCR-RFLP) technique. There were 2.51-fold [adjusted odds ratio (OR_adj), 2.51; 95% CI, 1.14-5.49; P = 0.02] and 2.49-fold (OR_adj, 2.49; 95% CI: 1.52-4.07; P < 0.01) increased risk of CBP for individuals carrying genotypes of hMTH1 83Val/Met + Met/Met and hOGG1 326Cys/Cys, respectively. Compared with individuals carrying genotypes of hOGG1 326Cys/Cys and hMYH 324His/His at the same time, there was a 0.33-fold (OR_adj, 0.33; 95% CI: 0.15-0.72; P < 0.05) decreased risk of CBP for those with genotypes of hOGG1 326Ser/Cys + Ser/Ser and hMYH 324His/Gln + Gln/Gln. In the smoking group, there was a 0.15-fold (OR_adj, 0.15; 95% CI, 0.03-0.68; P = 0.01) decreased risk of CBP for subjects carrying genotypes of hMYH 324His/Gln + Gln/Gln compared with those of genotype of hMYH 324His/His. Therefore, our results suggested that polymorphisms at codons 83 of hMTH1 and codon 326 of hOGG1 might contribute to CBP in a Chinese occupational population.     

Association of the genetic polymorphism of EPHX1 and EPHX2 with the susceptibility to chronic benzene poisoning

The aim of this study was to explore the association of the genetic polymorphism of EPHX1 and EPHX2 with the susceptibility to chronic benzene poisoning (CBP). A case-control study of 268 patients with CBP and 268 healthy workers matched by age and sex, all of whom were occupationally exposed to benzene, was conducted. The single nucleotide polymorphisms (SNPs, rs2854451, rs3738047, rs2234922 and rs1051741) of EPHX1 gene and the SNP (rs751141) of EPHX2 gene were tested by the TaqMan PCR method. In the subjects carrying the genotype of EPHX1 rs3738047 GG, the risk of CBP was decreased in the individuals simultaneously carrying EPHX1 rs2234922 G (P = 0.02). Alternatively, in the subjects carrying the genotype of EPHX1 rs2234922 AA, the risk of CBP was increased in the individuals simultaneously carrying the allele of EPHX2 rs751141A (P = 0.03). It was also found that there were potential interactions between alcohol consumption and the polymorphism of EPHX1 rs1051741 (χ_H ² = 5.28, P = 0.02) or rs2234922 (χ_H ² = 6.71, P = 0.01). Compared to individuals with EPHX1 rs1051741 CC or rs2234922 AA genotype in the drinkers, the risk of CBP in those carrying genotypes of EPHX1 rs1051741 CT+TT or rs2234922 AG+GG was decreased, respectively (P = 0.04, P < 0.01). Haplotype analysis of polymorphisms in EPHX1 showed that the risk of CBP was increased in the subjects with haplotype 2 (rs2854451-A, rs3738047-G, rs2234922-A, rs1051741-C) or haplotype 4 (rs2854451-G, rs3738047-A, rs2234922-G, rs1051741-T), but decreased in those with haplotype 6 (rs2854451-G, rs3738047-G, rs2234922-G, rs1051741-T) or haplotype 10 (rs2854451-A, rs3738047-A, rs2234922-G, rs1051741-T), respectively. Logistic regression analysis revealed that smoking might play a role in modifying the risk of CBP (OR = 0.313, 95% CI: 0.123–0.794, P = 0.015). The genetic polymorphism in EPHX1 may be associated with the risk of CBP in the Chinese occupational population and further research is needed for the association between the genetic polymorphism in EPHX2 and the susceptibility to CBP. Translated from Fudan University Journal of Medical Sciences, 2006, 33(4): 427–432 [译自: 复旦大学学报 (医学版)]     

Association between IL1B polymorphisms and the risk of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis dominated systemic disease with unknown etiology. The purpose of this study was to determine the relationship between IL1B polymorphisms and RA risk in a Chinese Han population. Four single-nucleotide polymorphisms (SNPs) of IL1B, rs2853550, rs1143643, rs3136558 and rs16944 were genotyped in 508 RA cases and 494 healthy controls using the Agena MassARRAY method. A genetic model analysis was performed to evaluate the relationships between the variants and RA risk. Haplotype analysis was used to evaluate the potential relationship between the genetic block and RA risk. We determined that rs1143643 was linked to a reduced risk of RA based on the results of the co-dominant model (OR = 0.67, 95%CI: 0.50–0.89, p = 0.006) and the dominant model (OR = 0.73, 95%CI = 0.56–0.96, p = 0.025). On the other hand, rs16944 was associated with an increased risk of RA in the co-dominant model (OR = 1.71, 95%CI = 1.53–1.97, p = 0.029) and the recessive model (OR = 1.41, 95%CI = 1.05–1.88, p = 0.021). Among individuals older than 50 years, we observed that rs2853550 was associated with an increased risk of RA, and that rs1143643 decreased RA risk. Furthermore, rs1143643 was associated with a decreased RA risk in female patients. However, rs16944 increased RA risk in both the co-dominant and the additive models in different age subgroups. In addition, rs16944-GA increased RA risk in males in the co-dominance model and rs16944-AA increased RA risk in females in the additive model. These results suggested that rs2853550, rs1143643, and rs16944 in the IL1B gene are associated with RA risk.     

CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls in elderly people

Objective The objective of this study is to investigate the association between CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls. Method Multivariate logistic regression was performed in an existing database in order to study the association between falls history and CYP2D6*4, CYP3A5*3, ABCB1 3435T polymorphisms in patients using fall-risk-increasing CYP2D6, CYP3A5 and P-glycoprotein (gene product of ABCB1) substrates. Results No statistically significant increased fall risk was found in ‘poor metabolizers’ compared to ‘extensive’ and ‘intermediate metabolizers’ using fall-risk-increasing CYP2D6 substrates (Odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.2–25.0), CYP3A5 substrates (OR = 0.9; 95% CI 0.2–3.3) and P-glycoprotein substrates (OR = 2.1; 95% CI 0.2–17.2). Conclusion The hypothesis that ‘poor metabolizers’ have an increased fall risk was not confirmed. A larger study population is needed to confirm the potential association that was seen between CYP2D6*4 and ABCB1 3435T polymorphisms and drug-related falls.     

Association of HLA-DP/DQ and STAT4 polymorphisms with ankylosing spondylitis in Southwest China

Ankylosing spondylitis (AS) is a highly heritable complex inflammatory arthritis disease. Genetic factors are thought to be crucial in the pathogenesis of AS. However, few data are available on the relationship between HLA-DP/DQ and STAT4 polymorphisms and AS susceptibility in the Chinese population. Therefore, we examined HLA-DP/DQ and STAT4 polymorphisms (rs3077, rs9277535, rs7453920 and rs7574865) in a total of 779 subjects, including 400 AS and 379 age- and sex-matched healthy controls in Chinese. No significant difference was observed between AS patients and healthy controls in the allele frequency of rs3077, rs9277535 and rs7574865. However, there was a significant association between the HLA-DQ rs7453920 G/A variant and AS patients, with minor allele A correlated with a reduced risk of AS (allelic frequency, adjusted OR = 0.66, 95% CI = 0.55–0.78, p = 4.0E − 06; dominant model, adjusted OR = 0.75, 95% CI = 0.66–0.85, p = 1.1E − 05). Moreover, the haplotypes block AAA and GGA in the HLA gene significantly correlated with reduced risk of AS. This is the first study demonstrating the significant associations of SNP rs7453920 and the haplotypes in the HLA gene with the risk of AS in Southwest Chinese population. This research sheds new light on the significant relationship between HLA polymorphisms and AS.     

IL-7R gene variants are associated with breast cancer susceptibility in Chinese Han women

BackgroundInterleukin 7 receptor (IL-7R) is a member of the type I cytokine receptor family, which affects the occurrence of various tumors by forming a signaling complex with its ligand Interleukin 7 (IL-7). This study aimed to explore the potential relationships of IL-7R polymorphisms with breast cancer susceptibility in the Chinese Han women.MethodsFive polymorphisms of IL-7R gene (rs969129, rs10213865, rs10053847, rs118137916, and rs6451231) form 553 patients and 550 healthy individuals among the Chinese Han women were genotyped using Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to evaluate the relationship.ResultsThe resulted of this study showed that rs10213865 was related to an increased breast cancer risk in allele (P = 0.045), dominant (P = 0.040), and log-additive (P = 0.029) models. As for rs969129, an increased risk of breast cancer was found in the allele (P = 0.018), co-dominant (P = 0.017), recessive (P = 0.034), and additive (P = 0.019) models. Rs6451231 was related to an increased risk of breast cancer under allele (P = 0.018), co-dominant (P = 0.021), and log-additive (P = 0.019) models. Age stratified analysis revealed that rs6451231 could enhance risk of breast cancer among the individuals older than 52 years. Furthermore, there was a significant correlation between haplotype C_rs969129G_rs10213865A_rs10053847G_rs118137916 and the decreased risk of breast cancer (P = 0.010).ConclusionsThis study firstly proved that IL-7R polymorphisms were significantly correlated with an increased susceptibility of breast cancer in the Chinese Han women.     

Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study

We report the results of a prospective randomised study to evaluate the therapeutic effect of Serenoa repens, Urtica dioica (ProstaMEV^®), quercitin and curcumin (FlogMEV^®) extracts associated with prulifloxacin in patients affected by chronic bacterial prostatitis (CBP). From a whole population of 284 patients, 143 patients affected by CBP [National Institutes of Health (NIH) class II prostatitis] were enrolled. All patients received prulifloxacin 600 mg daily for 14 days, in accordance with antibiogram results. Patients were split into two groups: Group A received prulifloxacin associated with ProstaMEV^® and FlogMEV^®; Group B received only antibiotic therapy. Microbiological and clinical efficacies were tested by two follow-up visits at 1 month and 6 months, respectively. Quality of life (QoL) was measured using the NIH Chronic Prostatitis Symptom Index (CPSI) and International Prostatic Symptom Score (IPSS) questionnaires. Group A comprised 106 patients and Group B comprised 37 patients. One month after treatment, 89.6% of patients who had received prulifloxacin associated with ProstaMEV^® and FlogMEV^® did not report any symptoms related to CBP, whilst only 27% of patients who received antibiotic therapy alone were recurrence-free (P < 0.0001). Significant differences were found between groups in terms of symptoms and QoL (P < 0.0001 for both). Six months after treatment, no patients in Group A had recurrence of disease whilst two patients in Group B did. Questionnaire results demonstrated statistically significant differences between groups (all P < 0.001). The association of S. repens, U. dioica (ProstaMEV^®), quercitin and curcumin (FlogMEV^®) extracts is able to improve the clinical efficacy of prulifloxacin in patients affected by CBP.     

小样本探讨黄嘌呤脱氢酶和鸟苷酸合成酶基因多态性对硫唑嘌呤所致骨髓抑制和脱发的影响

摘要：目的 研究黄嘌呤脱氢酶(Xanthine dehydrogenase,XDH)和鸟苷酸合成酶(Guanosine monophosphate synthetase,GMPS)基因多态性对硫唑嘌呤(Azathioprine,AZA)所致骨髓抑制和脱发的影响,探讨上述位点联合NUDT15 rs116855232检测对预测AZA所致骨髓抑制的价值。方法 回顾性分析曾经服用或正在服用AZA治疗自身免疫性疾病患者,收集静脉血采用直接测序法测定GMPS rs61750368、rs61750369,XDH rs2295475、rs1884725、rs17011368、rs566362和NUDT15 rs116855232基因型。依据不良反应进行分组,分析上述基因型与AZA所致骨髓抑制和脱发的相关性,NUDT15 rs116855232作为对照位点。结果 共纳入80例患者,2组在年龄、日剂量、疗程、BMI以及6-硫鸟嘌呤核苷酸浓度均无显著性差异(P＞0.05)。Logistic回归分析表明,AZA所致骨髓抑制与XDH rs229547突变相关(P=0.003, OR=3.10, 95% CI: 1.45~6.25),该基因预测骨髓抑制敏感度为69.6%,特异度为63.2%,ROC曲线AUC为0.66;NUDT15 rs116855232突变也和AZA所致骨髓抑制相关(P=0.008, OR=3.46, 95% CI: 1.21~9.93);其余位点基因型暂未发现与骨髓抑制和脱发相关。rs116855232野生型且rs2295475突变型的患者对比两位点野生型的患者,其骨髓抑制的危险值升高(OR=6.53, P=0.004),而两位点同时突变者骨髓抑制的危险值更高(OR=51.67, P＜0.001)。结论 在中国自身免疫性疾病患者中XDH rs2295475突变可能为AZA诱导骨髓抑制的独立危险因素,尽管预测准确度较低但仍有预测价值。尤其XDH联合NUDT15 rs116855232监测,可能会弥补NUDT15 野生型者对骨髓抑制预测不足的风险,提高NUDT15突变型对骨髓抑制预测的准确性,但以上结果还更多临床研究验证。     

VKORC1-3673G>A、CYP2C9*3、CYP4F2 rs2108622和CYP2C19*2基因多态性对中国汉族房颤患者华法林维持剂量的影响

目的 探讨VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622和CYP2C19^*2位点基因多态性对中国汉族房颤患者华法林维持剂量的影响。方法 收集107例服用华法林达维持剂量的汉族房颤患者的血样和临床相关资料,应用PCR-RFLP法检测VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622和CYP2C19^*2基因型,采用独立样本t检验分析基因型与华法林维持剂量的相关性。多元线性回归建立给药模型,探讨基因多态性对华法林维持剂量的影响。结果 VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622基因多态性和患者年龄、体质量能解释45.2%的华法林维持剂量差异。CYP2C19^*2基因多态性对本研究人群华法林维持剂量无影响。结论 VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622基因多态性显著影响中国汉族房颤患者的华法林维持剂量。     

Case‐control pharmacogenetic study of HCN1/HCN2 variants and genetic generalized epilepsies

Epilepsy is a common complex neurological disorder, and some forms are resistant to drug treatment. The HCN1/HCN2 genes encode hyperpolarization‐activated cyclic nucleotide‐gated channels, which play important roles in the electrophysiology of neurons. We investigated the association between HCN1/HCN2 variants and drug resistance or the risk of genetic generalized epilepsies (GGEs). We used matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry to assess nine variants of HCN1/HCN2 in 284 healthy participants and 483 GGEs (279 drug‐responsive, 204 drug‐resistant). Frequencies of HCN2 rs7255568 and rs3752158 G alleles differed in GGEs and in controls (P = .039, P = .027, respectively). The frequency of HCN2 haplotype (CAC) was higher in patients than controls (P = .046). The frequency of the HCN1 rs10462087 CC+CT genotype was lower in patients with childhood absence epilepsy (CAE) than controls (P = .047). Rs7255568 was associated with the risk of CAE (P = .028) and juvenile myoclonic epilepsy (JME) (P = .02). Rs3752158 was associated with the risk of generalized tonic‐clonic seizures, JME, and febrile seizures (all P < .05). The frequency of the HCN2 haplotype (CAC) was higher in patients with JME (P = .015) and in those with febrile seizures (P = .024) than in controls. No significant association was found between HCN1/HCN2 alleles, genotypes or haplotypes, and drug resistance in patients. After Bonferroni's multiple comparisons correction, only the HCN2 rs3752158 C allele and GC+CC genotype frequencies in patients with JME were higher than those in controls (19.2% vs 11.6%, odds ratio (OR) = 1.71, 95% CI = 1.18‐2.32), P = .004 < 0.05/9; 36% vs 22.2%, OR = 1.62(1.18‐2.23), P = .003 < 0.05/9). Our study suggests that HCN2 rs3752158 is involved in the susceptibility to JME.     

Association study of IL10 gene polymorphisms (rs1800872 and rs1800896) with cervical cancer in the Bangladeshi women

ObjectiveCervical cancer is one of the most destructive diseases among females worldwide, especially in developing countries. Interleukin-10 (IL10) is a multifunctional cytokine, and polymorphisms in the IL10 gene have been identified in multiple malignancies. However, no prior studies were conducted to determine the association of IL10 polymorphisms (rs1800872 and rs1800896) with cervical cancer patients in Bangladesh.MethodsThis case-control study was carried out on 240 cervical cancer patients and 204 healthy volunteers. Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR).ResultsIn the case of rs1800872, CA and AA genotypes significantly increased the risk of cervical cancer (OR = 1.59, 95% CI = 1.01–2.49, p = 0.043; OR = 2.75, 95% CI = 1.53–4.93, p = 0.0007, respectively) but the significance did not exist for CA genotype after Bonferroni correction (p < 0.025). An increased risk was also observed for the dominant model, recessive model, and allele model (A vs. C) of rs1800872 (dominant model: OR = 1.83, 95% CI = 1.18–2.80, p = 0.006; recessive model: OR = 2.00, 95% CI = 1.22–3.29, p = 0.006; allele model: OR = 1.55, 95% CI = 1.19–2.03, p = 0.001) which remained significant after the correction of Bonferroni. For rs1800896, only GG genotype and recessive model showed increased risk for cervical cancer (GG vs. AA: OR = 3.48, 95% CI = 1.46–8.31, p = 0.005; recessive model: OR = 3.57, 95% CI = 1.52–8.38, p = 0.003). These associations were statistically significant, and the significance existed after Bonferroni correction. Haplotype analysis revealed that AA haplotype significantly increased the risk (OR = 1.56, p = 0.001) whereas, CA haplotype significantly lowered the risk (OR = 0.42, p = 2.42x10^-8), and both rs1800872 and rs1800896 are strongly in linkage disequilibrium (D’=1, r² = 0.333). Moreover, the IL10 mRNA level was found up-regulated in silico in cervical squamous cell carcinoma tissues compared to healthy tissues (p = 1.11x10^-16).ConclusionOur study suggests that rs1800872 and rs1800896 polymorphisms of IL10 gene are associated with cervical cancer in Bangladeshi females.     

FOXO3 mutation predicting gefitinib-induced hepatotoxicity in NSCLC patients through regulation of autophagy

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.     

Safety of an injection with a mixture of extracts from Herba Artemisiae annuae, Fructus Gardeniae and Flos Lonicerae

Objective This study aimed to evaluate the safety for an injection with a mixture of extracts from Herba Artemisiae annuae, Fructus Gardeniae and Flos Lonicerae and to determine the risk factors that may affect its adverse drug reactions. Methods A drug-oriented prospective observational study was performed. Physicians filled in clinical observation forms with detailed information of the patients including general information, drug information, therapeutic effects and adverse drug events. The adverse drug reaction factors were analyzed by both mono-factor and multiple-factor logistic regression methods. Results From April to July 2007, we collected 12,427 observation forms from 46 hospitals in Jiangsu Province of China. Among the 11,707 observation forms we analyzed, 8,074 patients were children younger than 14 years old (69%). Among 51 reported adverse drug events, 45 cases were adverse drug reactions. The total adverse drug reaction incidence of the injection was 0.38%. While most adverse drug reactions were previously known (e.g., rash, pruritus, vomiting and diarrhea), we observed three new ADR symptoms: shiver, phlebitis and anhelation. All the adverse drug reactions were controlled very well through the follow-up therapy, and none of them was life threatening. The mono-factor analysis showed that adverse drug reactions of the injection were significantly correlated with total medication dose (P = 0.0049) and combination medication (P = 0.0143), especially with antimicrobial drugs (P = 0.0079) and macrolides (P = 0.0017). The multiple factor analysis confirmed these results: medication dosage and combination medication had a crucial impact on adverse drug reactions of the injection; the risk was increased by 24.8% (the estimated value of relative risk was 1.248, 95% confidence interval: 1.054–1.479) and 89% (1.890, 1.001–3.566), respectively. Conclusion The total adverse drug reaction incidence of the injection was 0.38% and lower than we expected. Moreover, we observed three new adverse drug reactions, none of which was severe.

Temporal trends, risk factors and outcomes in albicans and non-albicans candidaemia: an international epidemiological study in four multidisciplinary intensive care units

This multicentre study (i) evaluated geographic and temporal changes in candidaemia ecology in the critically ill, (ii) identified risk factors associated with non-albicans candidaemia and (iii) examined the association of Candida ecology with mortality. A retrospective cohort study of patients who developed candidaemia in four general Intensive Care Units located in Australia, Greece, Belgium and Brazil was performed. Two hundred Candida organisms were identified by positive blood culture in 189 patients, including 112 Candida albicans (56.0%), 38 Candida glabrata (19.0%), 21 Candida parapsilosis (10.5%), 18 Candida tropicalis (9.0%), 6 Candida krusei (3.0%), 1 Candida famata (0.5%), 1 Candida zeylanoides (0.5%) and 3 non-differentiated Candida spp. (1.5%). No trend towards increased non-albicans species over the study period (P = 0.68) or by geographic area (P = 0.35) was demonstrated. Independent risk factors for non-albicans candidaemia included: female gender [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.13–3.86] and increased central venous catheter days (OR 1.16 per 5-day interval, 95% CI 1.05–1.28). Mortality in the non-albicans group was non-significantly higher than in the albicans group (65% vs. 53%; P = 0.10). This study is unique in that a large number of intensive care candidaemias in four geographically diverse units have been studied.     

The influence of ABCB1 and P2Y12 genetic variants on clinical outcomes in Chinese intracranial artery stenosis patients

For intracranial artery stenosis patients, high inter‐individual variability in response to antiplatelet drug therapy results in recurrent ischaemic events. We aimed to evaluate the association of drug‐related genetic polymorphisms with adverse clinical outcomes. We consecutively enrolled 157 patients receiving dual‐antiplatelet therapy (aspirin plus clopidogrel), and adverse clinical events occurred in 10 patients during the 1 year follow‐up. The P2Y12 polymorphisms (rs9859538 and rs10935842) were associated with increased likelihood of relapse events (OR = 2.934, 95% CI = 1.022‐8.425, P‐value = .045), and the 2 variants are in complete linkage disequilibrium. The mutation of ABCB1 rs1128503 may decrease the recurrence of clinical events (OR = 0.211, 95% CI = 0.046‐0.957, P‐value = .044). Genetic testing (ABCB1 and P2Y12) may provide useful information to prevent ischaemic events prior to the initiation of antiplatelet therapy.     

基于循证医学方法研究儿童肺部侵袭性真菌感染的危险因素

目的 系统分析儿童侵袭性肺部真菌感染的相关危险因素，为临床治疗和感染管理提供循证医学证据。方法 检索PubMed、Embase、Cochrane Library、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、万方数据库以及维普信息资源系统（VIP）等数据库，收集儿童侵袭性真菌感染危险因素的临床对照研究，检索年限为2000年1月—2018年12月，按照NOS标准评价纳入研究的质量，meta分析提取数据。结果 纳入8个研究，7 203例患者，真菌感染组648例，非侵袭性真菌感染组6 555例。Meta分析显示，侵袭性真菌感染组的抗菌药物用药时间（MD=2.14，95%CI=1.42~2.87，P<0.001）和糖皮质激素用药时间（MD=1.60，95%CI=1.17~2.03，P<0.001）大于非真菌感染组，真菌感染组的危重病评分<70分（OR=3.18，95%CI=2.58~3.93，P<0.001）、抗菌药物用药时间>14 d （OR=3.22，95%CI=2.58~4.02，P<0.001）、糖皮质激素用药时间>7 d （OR=7.81，95%CI=5.63~10.83，P<0.001）、有创机械通气（OR=7.28，95%CI=4.72~11.21，P<0.001）、体内留置导管（OR=2.55，95%CI=2.06~3.14，P<0.001）、营养不良（OR=4.63，95%CI=3.11~6.91，P<0.001）及腹泻（OR=4.37，95%CI=3.38~5.65，P<0.001）的构成比大于非侵袭性真菌感染组。结论 按照关联强度，儿童侵袭性肺部真菌感染的危险因素依次为糖皮质激素用药时间>7 d、有创机械通气、营养不良、腹泻、抗菌药物用药时间>14 d、危重病评分<70分和体内留置导管。     

基因多态性与糖皮质激素诱导性股骨头坏死的相关性meta分析

目的 应用meta分析证实靶基因的多态性是否与糖皮质激素诱导性股骨头坏死（steroid-induced osteonecrosis of the femoral head,SONFH）发生相关。方法 检索PubMed、Embase、The Cochrane Library、Clinical Trial、CBM、万方、维普和CNKI等数据库中已发表的文章以获得适宜的研究,并以固定或者随机效应模型计算最终的OR值和95%置信区间（95%CI）。结果 检索共发现有37项研究包含41个与SONFH发生风险相关的基因多态性位点。选择含有≥3个适宜研究的多态性位点进入meta分析,纳入的多态性位点主要集中在3个基因即PAI-1、MTHFR和ABCB1。携带有PAI-1突变基因5G的患者应用糖皮质激素后易发生SONFH,但差异不具有统计学意义[OR=0.95,95%CI（0.54,1.67）,P=0.85]。SONFH发生率在MTHFR突变型和野生型之间差异存在统计学意义[OR=0.69,95%CI（0.50,0.95）,P=0.02],携带有MTHFR 677T的患者较易发生SONFH。携带ABCB1 3435C等位基因者发生SONFH的风险更高,具有显著的统计学差异[OR=1.40,95%CI（1.11,1.76）,P=0.005];而ABCB1 G2677T/A位点的基因多态性与SONFH发生之间无明显的统计学差异[OR=1.32,95%CI（0.76,2.28）,P=0.32]。结论 MTHFR C677T和ABCB1 C3435T基因的多态性与股骨头坏死的发生风险显著相关。     

Contribution of IL-7/7R genetic polymorphisms in coronary heart disease in Chinese Han population

BackgroundCoronary heart disease (CHD) is a common chronic inflammatory disease. Interleukin (IL)-7/IL-7R has been reported to be involved in the development of CHD. However, the relationship between IL-7/7R genetic polymorphisms and CHD among the Han Chinese population remains unclear.MethodsTo examine whether IL-7/7R variants contributed to CHD, six single-nucleotide polymorphisms (SNPs) were genotyped by using the Agena MassARRAY platform in 499 CHD patients and 496 controls. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). The linkage disequilibrium was analyzed using Haploview software. The association between clinical parameters and IL-7/7R polymorphisms was determined by a one-way ANOVA.ResultsIL-7R rs969129 G (OR = 1.20, 95% CI: 1.00–1.43, p = 0.047) allele and GG (OR = 1.45, 95% CI: 1.01–2.08, p = 0.044) genotype carriers had a higher risk for CHD. IL-7R haplotype “ACAG” (OR = 1.43, 95% CI: 1.09–1.87, p = 0.010) conferred an increased CHD risk. Rs969129, rs6451231, and rs117173992 were related to CHD susceptibility in males and/or the subgroup of individuals aged >61 years. IL-7R rs969129, rs10053847, rs6451231, and rs118137916 variants were associated with diabetes in patients with CHD. Moreover, rs969129, rs6451231, and rs117173992 were associated with high-density lipoprotein cholesterol (HDL-C) concentrations, whereas rs118137916 and rs10053847 were associated with low-density lipoprotein cholesterol (LDL-C) levels (p < 0.05).ConclusionIL-7/7R variants were related to the genetic predisposition of CHD in the Chinese Han population. These findings increase our knowledge regarding the effect of IL-7/7R on CHD.