Immunoprofiling of Equine Plasma against Deinagkistrodon acutus in Taiwan: Key to Understanding Differential Neutralization Potency in Immunized Horses.

Snakebite envenoming is a public health issue linked to high mortality and morbidity rates worldwide. Although antivenom has been the mainstay treatment for envenomed victims receiving medical care, the diverse therapeutic efficacy of the produced antivenom is a major limitation. Deinagkistrodon acutus is a venomous snake that poses significant concern of risks to human life in Taiwan, and successful production of antivenom against D. acutus envenoming remains a considerable challenge. Among groups of horses subjected to immunization schedules, few or none subsequently meet the quality required for further scale-up harvesting. The determinants underlying the variable immune responses of horses to D. acutus venom are currently unknown. In this study, we assessed the immunoprofiles of high-potency and low-potency horse plasma against D. acutus venom and explored the conspicuous differences between these two groups. Based on the results of liquid chromatography with tandem mass spectrometry (LC-MS/MS), acutolysin A was identified as the major component of venom proteins that immunoreacted differentially with the two plasma samples. Our findings indicate underlying differences in antivenoms with variable neutralization efficacies, and may provide valuable insights for improvement of antivenom production in the future.

LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. METHODS: Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. RESULTS: LINC01414 rs699467 (OR = 0.73, 95% CI 0.56-0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31-0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31-6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). CONCLUSION: Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population / Influencia de los polimorfismos del gen CYP2J2 en el riesgo de desarrollo de enfermedad pulmonar obstructiva crónica en la población Han China

INTRODUCTION: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility. MATERIAL AND METHODS: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk. RESULTS: We observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01-0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01-0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01-0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01-0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13-2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15-2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09-1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (Ars11207535Crs10889159Trs1155002 and Ars11207535Crs10889159Crs1155002) significantly decreased COPD risk. CONCLUSION: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population

INTRODUCCIÓN: El citocromo P450 (CYP) 2J2 es una enzima importante que controla la biosíntesis de los ácidos epoxieicosatrienoicos, y que podría desempeñar un papel en el desarrollo de la enfermedad pulmonar obstructiva crónica (EPOC). En este estudio, nuestro objetivo fue evaluar la influencia de los polimorfismos de CYP2J2 en la susceptibilidad a la EPOC. MATERIALES Y MÉTODOS: Se realizó un estudio de casos y controles que incluyó 313 casos de EPOC y 508 controles para investigar la asociación entre los polimorfismos de CYP2J2 y el riesgo de desarrollar EPOC. Se utilizó la plataforma Agena MassARRAY para genotipar los polimorfismos de CYP2J2. Se calcularon los odds ratio (OR) con unos intervalos de confianza (IC) del 95% para valorar la asociación entre los polimorfismos de CYP2J2 y el riesgo de la EPOC. RESULTADOS: Observamos que rs11207535 (homocigoto: OR: 0,08, IC 95%: 0,01-0,96; p = 0,047; recesivo: OR: 0,08; IC 95%: 0,01-0,94; p = 0,044), rs10889159 (homocigoto: OR: 0,08, IC 95%: 0,01-0,92; p = 0,043; recesivo: OR: 0,08, IC 95%: 0,01-0,90; p = 0,040) y rs1155002 (heterocigoto: OR: 1,63, IC 95%: 1,13-2,36; p = 0,009; dominante: OR: 1,64, IC 95%: 1,15-2,35; p = 0,006; aditivo: OR: 1,45, IC 95%: 1,09-1,92; p = 0,011) se asociaron significativamente con el riesgo de EPOC. Las pruebas alélicas mostraron que el alelo T de rs2280274 estaba relacionado con una disminución del riesgo de EPOC y el alelo T de rs1155002 se asoció con un mayor riesgo de EPOC. Los análisis estratificados indicaron que los efectos de los polimorfismos de CYP2J2 y el riesgo de EPOC dependían del sexo y del tabaquismo (p < 0,05). Además, 2 haplotipos (Ars11207535Crs10889159Trs1155002 y Ars11207535Crs10889159Crs1155002) reducían significativamente el riesgo de la EPOC. CONCLUSIÓN: El estudio sugirió que los polimorfismos de CYP2J2 se asociaban con la susceptibilidad a la EPOC en la población Han China

The effect of CYP3A4 genetic variants on the susceptibility to chronic obstructive pulmonary disease in the Hainan Han population.

PURPOSE: Genetic polymorphisms act a crucial role in chronic obstructive pulmonary disease (COPD) progression. This study aimed to investigate the correlation between CYP3A4 variants and COPD risk. METHODS: We carried out a case-control study of 821 individuals (313 patients and 508 healthy subjects) to identify the correlation of CYP3A4 SNPs with COPD risk in the Hainan Han population. The association was evaluated by Odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Our study showed that rs4646437 polymorphism was related to a significantly increased susceptibility to COPD (OR 1.45, 95% CI = 1.10-1.90, p = 0.008). Stratified analyses indicated that rs4646437 polymorphism was significantly related to an increased risk of COPD in males (OR 1.95, 95% CI = 1.19-3.20, p = 0.008). However, rs4646440 played a protective role in females (OR 0.54, 95% CI = 0.31-0.93, p = 0.024). Rs4646437 was found to significantly improve the risk of COPD in smokers (OR 1.67, 95% CI = 1.12-2.48, p = 0.011). While rs4646440 had a significantly lower susceptibility to COPD in non-smokers (OR 0.64, 95% CI = 0.45-0.90, p = 0.010). Haplotype analysis revealed that Ars4646440Trs35564277 haplotype of CYP3A4 was found to increase the risk of COPD in non-smokers (OR 1.71, 95% CI = 1.04-2.82, p = 0.034). CONCLUSION: Our result gives a new understanding of the association between CYP3A4 gene and COPD in the Hainan Han population.

Genetic Polymorphisms of CYP2C9/CYP2C19 in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a high incidence in the elderly and significantly affects the quality of life. CYP2C9 and CYP2C19 play an important role in tobacco-related diseases and inflammatory reactions. Thus, we aim to investigate the association between CYP2C9/CYP2C19 polymorphisms and the risk of COPD. In this study, a total of 821 subjects were recruited which include 313 COPD cases and 508 healthy controls. Seven SNPs of CYP2C9/CYP2C19 were selected for genotyping. The odds ratios (ORs) and 95% confidence interval (95% CI) were calculated using logistic regression analysis to evaluate the association between COPD risk and CYP2C9/CYP2C19 polymorphisms. Our study showed that A allele of rs9332220 in CYP2C9 was associated with reducing COPD risk (OR = 0.64, 95% CI = 0.43-0.94, p = 0.021). And rs111853758 G allele carrier could significantly decrease 0.35-fold COPD risk compared with T allele carrier (OR = 0.65, 95% CI = 0.45-0.96, p = 0.027). Furthermore, sex-based stratification analysis showed that rs9332220 and rs111853758 polymorphisms were associated with the risk of COPD in males. This is the first study to investigate the association between CYP2C9 and CYP2C19 genetic polymorphisms and COPD risk, which may give a new perspective on the prevention and diagnosis of COPD.

The correlation between CYP4F2 variants and chronic obstructive pulmonary disease risk in Hainan Han population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disease. Cytochrome P450 family 4 subfamily F member 2 (CYP4F2) belongs to cytochrome P450 superfamily of enzymes responsible for metabolism, its single nucleotide polymorphisms (SNPs) were reported to be involved in metabolism in the development of many diseases. The study aimed to assess the relation between CYP4F2 SNPs and COPD risk in the Hainan Han population. METHOD: We genotyped five SNPs in CYP4F2 in 313 cases and 508 controls by Agena MassARRAY assay. The association between CYP4F2 SNPs and COPD risk were assessed by χ2 test and genetic models. Besides, logistic regression analysis was introduced into the calculation for odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Allele model analysis indicated that rs3093203 A was significantly correlated with an increased risk of COPD. Also, rs3093193 G and rs3093110 G were associated with a reduced COPD risk. In the genetic models, we found that rs3093203 was related to an increased COPD risk, while rs3093193 and rs3093110 were related to a reduced risk of COPD. After gender stratification, rs3093203, rs3093193 and rs3093110 showed the association with COPD risk in males. With smoking stratification, rs3093144 was significantly associated with an increased risk of COPD in smokers. CYP4F2 SNPs were significantly associated with COPD risk. CONCLUSIONS: Our findings illustrated potential associations between CYP4F2 polymorphisms and COPD risk. However, large-scale and well-designed studies are needed to determine conclusively the association between the CYP4F2 SNPs and COPD risk.

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population.

INTRODUCTION: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility. MATERIAL AND METHODS: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk. RESULTS: We observed rs11207535 (homozygote: OR=0.08, 95%CI=0.01-0.96, p=0.047; recessive: OR=0.08, 95%CI=0.01-0.94, p=0.044), rs10889159 (homozygote: OR=0.08, 95%CI=0.01-0.92, p=0.043; recessive: OR=0.08, 95%CI=0.01-0.90, p=0.040) and rs1155002 (heterozygote: OR=1.63, 95%CI=1.13-2.36, p=0.009; dominant: OR=1.64, 95%CI=1.15-2.35, p=0.006; additive: OR=1.45, 95%CI=1.09-1.92, p=0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p<0.05). Additionally, two haplotypes (Ars11207535Crs10889159Trs1155002 and Ars11207535Crs10889159Crs1155002) significantly decreased COPD risk. CONCLUSION: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.

CYP2B6 genetic polymorphisms influence chronic obstructive pulmonary disease susceptibility in the Hainan population.

Introduction: Chronic obstructive pulmonary disease (COPD) is a lung disease closely related to exposure to exogenous substances. CYP2B6 can activate many exogenous substances, which in turn affect lung cells. The aim of this study was to assess the association of single-nucleotide polymorphisms (SNPs) in CYP2B6 with COPD risk in a Chinese Han population. Materials and methods: Genotypes of the five candidate SNPs in CYP2B6 were identified among 318 cases and 508 healthy controls with an Agena MassARRAY method. The association between CYP2B6 polymorphisms and COPD risk was evaluated using genetic models and haplotype analyses. Results: In allele model, we observed that rs4803420 G and rs1038376 A were related to COPD risk. And rs4803420 G/T and G/T-T/T were related to a decreased COPD risk compared to GG genotype in the co-dominant and dominant models, respectively. When comparing with the AA genotype, rs1038376 A/T and A/T-T/T were associated with an increased COPD risk in the co-dominant and dominant models, respectively. Further gender stratification co-dominant and dominant models analysis showed that genotype G/T and G/T-T/T of rs4803420, and genotype A/T and A/T-T/T of rs1038376 were significantly associated with COPD risk compared to the wide type in males and females, while allele C of rs12979270 was only associated with COPD risk in females. Smoking status stratification analysis showed that rs12979270 C was significantly associated with an increased COPD risk under the allele model compared with allele A in the smoking subgroup. Haplotype analysis showed that haplotype GTA and TAA were related to COPD risk. Conclusion: Our data is the first to demonstrate that CYP2B6 polymorphisms may exert effects on COPD susceptibility in the Chinese Han population.