BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Humans ; Transcriptome/genetics* ; East Asian People ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Pulmonary Disease, Chronic Obstructive/genetics* ; Polymorphism, Single Nucleotide/genetics*

BACKGROUND: A polygenic risk score (PRS) derived from 112 single-nucleotide polymorphisms (SNPs) for gastric cancer has been reported in Chinese populations (PRS-112). However, its performance in other populations is unknown. A functional PRS (fPRS) using functional SNPs (fSNPs) may improve the generalizability of the PRS across populations with distinct ethnicities. METHODS: We performed functional annotations on SNPs in strong linkage disequilibrium (LD) with the 112 previously reported SNPs to identify fSNPs that affect protein-coding or transcriptional regulation. Subsequently, we constructed an fPRS based on the fSNPs by using the LDpred2-infinitesimal model and then analyzed the performance of the PRS-112 and fPRS in the risk prediction of gastric cancer in 457,521 European participants of the UK Biobank cohort. Finally, the performance of the fPRS in combination with lifestyle factors were evaluated in predicting the risk of gastric cancer. RESULTS: During 4,582,045 person-years of follow-up with a total of 623 incident gastric cancer cases, we found no significant association between the PRS-112 and gastric cancer risk in the European population (hazard ratio [HR] = 1.00 [95% confidence interval (CI) 0.93-1.09], P = 0.846). We identified 125 fSNPs, including seven deleterious protein-coding SNPs and 118 regulatory non-coding SNPs, and used them to construct the fPRS-125. Our result showed that the fPRS-125 was significantly associated with gastric cancer risk (HR = 1.11 [95% CI, 1.03-1.20], P = 0.009). Compared to participants with a low fPRS-125 (bottom quintile), those with a high fPRS-125 (top quintile) had a higher risk of incident gastric cancer (HR = 1.43 [95% CI, 1.12-1.84], P = 0.005). Moreover, we observed that participants with both an unfavorable lifestyle and a high genetic risk had the highest risk of incident gastric cancer (HR = 4.99 [95% CI, 1.55-16.10], P = 0.007) compared to those with both a favorable lifestyle and a low genetic risk. CONCLUSION These results indicate that the fPRS-125 derived from fSNPs may act as an indicator to measure the genetic risk of gastric cancer in the European population.
Humans ; Prospective Studies ; Stomach Neoplasms/genetics* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Multifactorial Inheritance/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Genome-Wide Association Study

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. METHODS: A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. RESULTS: The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. CONCLUSIONS Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Humans ; Middle Aged ; Young Adult ; Genotype ; Neutrophils ; Plasminogen Activator Inhibitor 1/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Retrospective Studies ; Sepsis/genetics*

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

OBJECTIVE: To assess the association of cytochrome P450 (CYP450) gene polymorphisms with the occurrence of ischemic stroke (IS). METHODS: From January 2020 to August 2022, 390 IS patients treated at the Zhengzhou Seventh People's Hospital were enrolled as the study group, and 410 healthy individuals undergoing physical examination during the same period were enrolled as the control group. Clinical data of all subjects were collected, which included age, sex, body mass index (BMI), smoking history and results of laboratory tests. Chi-square test and independent sample t test were used for comparing the clinical data. Multivariate logistic regression analysis was used to analyze the non-hereditary independent risk factors for IS. Fasting blood samples of the subjects were collected, and the genotypes of rs4244285, rs4986893, rs12248560 of the CYP2C19 gene and rs776746 of the CYP3A5 gene were determined by Sanger sequencing. The frequency of each genotype was calculated by using SNPStats online software. The association between the genotype and IS under the dominant, recessive and additive models was analyzed. RESULTS: The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), apolipoprotein B (Apo-B) and homocysteine (Hcy) of the case group were significantly higher than those of the control group, whilst the levels of high density lipoprotein (HDL-C) and Apo-A1 (APO-A1) were significantly lower (P < 0.05). Multivariate Logistic regression analysis showed that TC (95%CI = 1.13-1.92, P = 0.02), LD-C (95%CI = 1.03-2.25, P = 0.03), Apo-A1 (95%CI = 1.05-2.08, P = 0.04), Apo-B (95%CI = 1.7-4.22, P < 0.01) and Hcy (95%CI = 1.12-1.83, P = 0.04) were non-genetic independent risk factors for the occurrence of IS. Analysis of the association between the genetic polymorphisms and the risk of IS showed that the AA genotype at rs4244285 of the CYP2C19 gene, the AG genotype and A allele at rs4986893 of the CYP2C19 gene, and the GG genotype and G allele at rs776746 of the CYP3A5 gene were significantly associated with IS. Under the recessive/additive model, dominant model and dominant/additive model, polymorphisms of the rs4244285, rs4986893 and rs776746 loci were also significantly associated with the IS. CONCLUSION TC, LDL-C, Apo-A1, Apo-B and Hcy can all affect the occurrence of IS, and CYP2C19 and CYP3A5 gene polymorphisms are closely associated with the IS. Above finding has confirmed that the CYP450 gene polymorphisms can increase the risk of IS, which may provide a reference for the clinical diagnosis.
Humans ; Cytochrome P-450 CYP3A/genetics* ; Cytochrome P-450 CYP2C19/genetics* ; Ischemic Stroke ; Cholesterol, LDL/genetics* ; Polymorphism, Single Nucleotide ; Genotype ; Apolipoproteins B/genetics* ; Gene Frequency

Sleep has attracted extensive attention due to its significance in health. However, its association with erectile dysfunction (ED) is insufficiently investigated. To investigate the potential causal links between sleep traits (insomnia, sleep duration, and chronotype) and ED, this study was performed. The single-nucleotide polymorphisms (SNPs) associated with insomnia, sleep duration, and chronotype were retrieved from previous genome-wide association studies (GWAS). A conventional two-sample Mendelian randomization (MR) was used to estimate the causal links between sleep traits and ED. The summary statistics of ED were from individuals of European ancestry (6175 cases vs 217 630 controls). As shown by the random effect inverse-variance-weighting (IVW) estimator, genetically predicted insomnia was causally associated with a 1.15-fold risk of ED (95% confidence interval: 1.07-1.23, P < 0.001). Sleep duration and morningness were not causally associated with ED, as indicated by the IVW (all P > 0.05). These findings were consistent with the results of sensitivity analyses. Based on genetic data, this study provides causal evidence that genetically predicted insomnia increases the risk of ED, whereas sleep duration and chronotype do not.
Male ; Humans ; Sleep Initiation and Maintenance Disorders/genetics* ; Genome-Wide Association Study ; Erectile Dysfunction/genetics* ; Sleep/genetics* ; Phenotype ; Polymorphism, Single Nucleotide

OBJECTIVE: To investigate the correlation between single-nucleotide polymorphism (SNP) of ARID5B gene and resistance to methotrexate (MTX) in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 144 children with ALL who were treated in General Hospital of Ningxia Medical University from January 2015 to November 2021 were enrolled and divided into MTX resistant group and non-MTX resistant group, with 72 cases in each group. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technology was used to measure the SNP of ARID5B gene in all children and analyze its correlation with MTX resistant. RESULTS: There were no significant differences in the genotype and gene frequency of rs7923074, rs10821936, rs6479778, and rs2893881 between MTX resistant group and non-MTX resistant group (P>0.05). The frequency of C/C genotype in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T/T genotype was opposite (P<0.05). The frequency of C allele in the MTX resistant group was significantly higher than that in the non-MTX resistant group, while the frequency of T allele was opposite (P<0.05). Multivariate logistic regression analysis showed that ARID5B gene rs4948488 TT genotype and T allele frequency were risk factors for MTX resistant in ALL children (P<0.05). CONCLUSION The SNP of ARID5B gene is associated with MTX resistant in ALL children.
Child ; Humans ; DNA-Binding Proteins/genetics* ; Gene Frequency ; Genotype ; Methotrexate ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Transcription Factors/genetics* ; Drug Resistance, Neoplasm

Objective: To investigate the association of circulating sPD-1 level and PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma. Methods: A case-control study was conducted. A total of 237 chronic HBV infection cases and 138 HBV infection-associated hepatocellular carcinoma in the Department of Infectious Diseases of the First Hospital of Shanxi Medical University from 2018 to 2021 were selected as the case group. About 250 individuals who visited a hospital physical examination center for routine physical examination during the same period were selected as the control group. Plasma sPD-1 levels were measured by using an ELISA kit and genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The association of sPD-1 levels and PD-1 polymorphisms with HBV infection as well as HBV infection-associated hepatocellular carcinoma was analyzed by using logistic regression models after adjusting for age, sex, alcohol consumption, smoking, ALT and AST levels. The sPD-1 level and PD-1 polymorphisms were independent variables, and HBV infection was the dependent variable. Results: The age of 237 chronic HBV infections, 138 HBV infection-related liver cancer case subjects and 250 control subjects in the study was (49.1±10.8), (51.9±12.7) and (50.7±11.9) years, respectively. Multivariate logistic regression model analysis showed that with a 1 pg/ml increase in sPD-1 level, the OR (95%CI) values for the risk of incident HBV infection cases and HBV hepatocellular carcinoma cases were 1.92 (1.68-2.19) and 2.02 (1.69-2.40). For rs2227981, compared with the CC genotype, the TT genotype had a lower risk of HBV infection and liver cancer associated with HBV infection, with OR (95%CI) values of 0.45 (0.22-0.91) and 0.35 (0.14-0.91). For rs2227982, compared with the CC genotype, the CT and TT genotypes also had a lower risk of HBV infection [OR (95%CI) values of 0.72 (0.53-0.97) and 0.57 (0.35-0.93)] and HBV infection-related liver cancer [OR (95%CI) values of 0.64 (0.45-0.92) and 0.52 (0.29-0.93)]. Conclusions: Plasma sPD-1 levels and PD-1 gene polymorphisms are associated with HBV infection and HBV infection-associated hepatocellular carcinoma.
Humans ; Carcinoma, Hepatocellular/genetics* ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Hepatitis B virus/genetics* ; Liver Neoplasms/genetics* ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Programmed Cell Death 1 Receptor/genetics* ; Adult ; Middle Aged

Objective: To analyze the genetic characteristics of varicella-zoster virus (VZV) in people aged 20 years and under in Yichang City of Hubei Province from 2019 to 2020. Methods: Based on the Yichang Health Big Data Platform, we investigated cases 20 and under clinically diagnosed as herpes zoster in three hospitals from March 2019 to September 2020. Collecting vesicle fluid and throat swab samples of the cases and completing questionnaires to obtain basic information. Real-time fluorescent quantitative PCR was used for positive identification of the virus. PCR amplification of VZV's open reading frame (ORF) and sequencing of the products to determine the VZV genotype. Analyze mutations at some specific single nucleotide polymorphism (SNP) sites. Results: Among 46 cases of herpes zoster, the male to female ratio was 1.3∶1 (26∶20) and the age ranged from 7 to 20 years old. Fifteen cases had been vaccinated against varicella, including 13 and 2 cases of 1 and 2 doses, respectively. VZV strains were detected in 34 samples (73.91%), all belonging to Clade 2. Phylogenetic tree analysis of the nucleotide of ORF22 showed, compared with Clade 2 referenced strains, the sequence matching degree of nucleotide for all 34 samples was 99.0% to 100.0%. Conclusion: The main VZV strain causing herpes zoster in people aged 20 years and under in Yichang from 2019 to 2020 was Clade 2.
Humans ; Child ; Adolescent ; Young Adult ; Adult ; Herpesvirus 3, Human/genetics* ; Phylogeny ; Herpes Zoster/epidemiology* ; Polymorphism, Single Nucleotide ; Real-Time Polymerase Chain Reaction ; Nucleotides