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DEFB126 polymorphisms and association with idiopathic asthenozoospermia in China

Asian Journal of Andrology 2022年第6期24卷 607-614页

作者： Jiao-Yu He Jian-Ying Peng Qiu-Fu Li Xiao-Li Lin Yan-Ru Cui Shi-Yu Ma Shi-Yun Fan Yi-Ran Liu Zhi-Lin Song Jun-Hang Deng Xia Wei Xian-Ping Ding Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education College of Life SciencesSichuan UniversityChengdu 610065China Chongqing Nanchuan Biotechnology Research Institute Bio-resource Research and Utilization Joint Key Laboratory of Sichuan and ChongqingChongqing 400000China

Idiopathic asthenozoospermia,a common factor in male infertility,is characterized by altered sperm motility function in fresh ejaculate.Although theβ-defensin 126(DEFB126)protein is associated with asthenozoospermia,DEFB126 gene polymorphisms have not been extensively studied.Therefore,the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation.Screening was performed by semen analysis,karyotype analysis,and Y microdeletion detection,and 102 fertile men and 106 men with asthenozoospermia in Chengdu,China,were selected for DEFB126 gene sequence analyses.Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected.rs11467417(317-318 del/del),rs11467497(163-166 wt/del),c.152T>C,and c.227A>G were significantly different between the control and asthenozoospermia groups,likely representing high-risk genetic factors for asthenozoospermia among males.DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion.The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus,and the rs11467417 binucleotide deletion produces a non-stop messenger RNA(mRNA).The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces.Based on in silico analysis,the amino acids 51M and 76K are located in the highly conserved domain;c.152T>C(M51T)and c.227A>G(K76R)are predicted to be damaging and capable of changing alternative splice,structural and posttranslational modification sites of the RNA,as well as the secondary structure,structural stability,and hydrophobicity of the protein,suggesting that these mutations are associated with asthenozoospermia.

关键词： β-defensin 126 idiopathic asthenozoospermia in silico analysis single-nucleotide polymorphisms

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Pathogenesis of premature coronary artery disease:Focus on risk factors and genetic variants

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Genes & Diseases 2022年第2期9卷 370-380页

作者： Haiming Wang Zifan Liu Junjie Shao Min Jiang Xuechun Lu Lejian Lin Lin Wang Qiang Xu Haomin Zhang Xin Li Jingjing Zhou Yundai Chen Ran Zhang Department of Cardiovascular Medicine Chinese PLA General Hospital&Chinese PLA Medical SchoolBeijing 100853PR China The First Clinical Medical College of Inner Mongolia Medical University Hohhot 010059PR China Department of Hematology The Second Medical Center of Chinese PLA General Hospital&Chinese PLA Medical SchoolBeijing 100853PR China Department of Health Services The First Medical Center of Chinese PLA General Hospital&Chinese PLA Medical SchoolBeijing 100853PR China

The development of premature coronary artery disease(PCAD)is dependent on both genetic predisposition and traditional risk factors.Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies.Genome-wide association studies(GWASs)have identified a considerable number of common genetic variants that are associated with PCAD.Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms(SNPs).The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity.Some characteristic genetic variants have been identified in Chinese populations.Although translating this genetic knowledge into clinical applications is still challenging,these genetic variants can be used for CAD phenotype identification,genetic prediction and therapy.In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD.We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.

关键词： Genetic clinical applications Genetic variants Genome-wide association studies Premature coronary artery disease single-nucleotide polymorphisms

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Causal Association Between Tea Consumption and Gout:A Mendelian Randomization Study

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Current Medical Science 2023年第5期43卷 947-954页

作者： Qi WANG Yi-ning LIU Hui ZHANG Ze-qun ZHANG Xiu-ying HUANG Wen-ze XIAO Shanghai Pudong Hospital Fudan University Pudong Medical CenterShanghai 201399China Human Phenome Institute Zhangjiang Fudan International Innovation CentreFudan UniversityShanghai 200433China Department of Emergency Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Department of Rheumatology Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China

Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization(MR).Methods Genome-wide association studies in UK Biobank included 349376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day.Summary statistics from the Chronic Kidney Disease Genetics consortium included 13179 cases and 750634 controls for gout.Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk.The inverse-variance weighted(IVW)method was used for primary analysis,and sensitivity analyses were also conducted to validate the potential causal effect.Results In this study,the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method(OR:0.90;95%CI:0.82–0.98).Similar results were found in weighted median methods(OR:0.88;95%CI:0.78–1.00),while no significant associations were found in MR-Egger(OR:0.89;95%CI:0.71–1.11),weighted mode(OR:0.80;95%CI:0.65–0.99),and simple mode(OR:1.01;95%CI:0.75–1.36).In addition,no evidence of pleiotropy was detected by MR-Egger regression(P=0.95)or MR-PRESSO analysis(P=0.07).Conclusion This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.

关键词： tea consumption gout single-nucleotide polymorphisms Mendelian randomization

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Polymorphism AGT2(rs4762)is involved in the development of dermatologic events:Proof-of-concept in hepatocellular carcinoma patients treated with sorafenib

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World Journal of Hepatology 2022年第7期14卷 1438-1458页

作者： Víctor Sapena Massimo Iavarone Loreto Boix Floriana Facchetti Maria Guarino Marco Sanduzzi Zamparelli Alessandro Granito Esther Samper Mario Scartozzi Josep Corominas Giorgia Marisi Alba Díaz Andrea Casadei-Gardini Laura Gramantieri Pietro Lampertico Filomena Morisco Ferran Torres Jordi Bruix María Reig Barcelona Clinic Liver Cancer Group Liver UnitHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi SunyerCentro de Investigación Biomédica en Red Enfermedades Hepáticas y DigestivasBarcelona 08036Spain Universidad de Barcelona Barcelona 08036Spain Division of Gastroenterology and Hepatology Foundation Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Ca’Granda Ospedale Maggiore PoliclinicoMilano 20122Italy Department of Clinical Medicine and Surgery Gastroenterology UnitUniversity of Naples Federico IINaples 80131Italy Gastroenterology and Hepatology Unit Fondazione Istituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica CàGranda Ospedale Maggiore PoliclinicoUniversity of MilanMilan 20100Italy Department of Clinical Medicine and Surgery Gastroenterology UnitUniversity of Naples"Federico II"Napoli 80100Italy Department of Clinical Medicine and Surgery Gastroenterology and HepatologyFederico II University of NaplesNaples 80131Italy Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Azienda Ospedaliero-Universitaria di BolognaBologna 40139Italy Department of Medical and Surgical Sciences University of BolognaBologna 40139Italy Department of Medical Oncology University of CagliariCagliari 45698Italy Biosciences Laboratory Istituto di Ricovero e Cura a Carattere Scientifico di Natura PubblicaIstituto Romagnolo per lo Studio dei Tumori“Dino Amadori”Meldola 47014Italy Department of Pathology Hospital Clínic de BarcelonaUniversitat de BarcelonaBarcelona 08036Spain School of Medicine Vita-Salute San Raffaele UniversityMilan 20132Italy Unit of Oncology UniversitàVita-SaluteIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica-San Raffaele Scientific InstituteMilan 20132Italy Division of Internal Medicine Hepatobiliary and Immunoallergic DiseasesIstituto di Ricovero e Cura a Carattere Scientifico di Natura Pubblica Aziend

BACKGROUND Dermatologic adverse events(DAEs)are associated with a better outcome in patients with hepatocellular carcinoma(HCC)irrespective of the therapeutic agent received.The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors(TKIs)to the skin or an immune-mediated reaction triggered by the oncologic treatment.As is the case in other conditions,individual genetic variants may partially explain a higher risk of DAEs.AIM To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with TKIs.METHODS We first analyzed 27 single-nucleotide polymorphisms(SNPs)from 12 genes selected as potential predictors of adverse event(AE)development in HCC patients treated with sorafenib[Barcelona Clinic Liver Cancer 1(BCLC1)cohort].Three additional cohorts were analyzed for AGT1(rs699)and AGT2(rs4762)polymorphisms-initially identified as predictors of DAEs:BCLC2(n=79),Northern Italy(n=221)and Naples(n=69)cohorts,respectively.The relation between SNPs and DAEs and death were assessed by univariate and multivariate Cox regression models,and presented with hazard ratios and their 95%confidence intervals(95%CI).RESULTS The BCLC1 cohort showed that patients with arterial hypertension(AHT)(HR=1.61;P value=0.007)and/or AGT SNPs had an increased risk of DAEs.Thereafter,AGT2(rs4762)AA genotype was found to be linked to a statistically significant increased probability of DAEs(HR=5.97;P value=0.0201,AA vs GG)in the Northern Italy cohort by multivariate analysis adjusted for BCLC stage,ECOG-PS,diabetes and AHT.The value of this genetic marker was externally validated in the cohort combining the BCLC1,BCLC2 and Naples cohorts[HR=3.12(95%CI:1.2-8.14),P value=0.0199,AGT2(rs4762)AA vs AG genotype and HR=2.73(95%CI:1.18-6.32)P value=0.0188,AGT2(rs4762)AA vs GG genotype].None of the other gene variants tested were found to be associated with the risk of DAE development.CONCLUSION DAE development in HCC

关键词： HCC Early DAE single-nucleotide polymorphisms AGT1(rs699) AGT2(rs4762),Tyrosine kinase inhibitors

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Reveal the Population Genetic Characteristics of Bombay Duck (Harpadon nehereus) in Coastal Waters of China with Genotyping-by-Sequencing Technique

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Journal of Ocean University of China 2022年第5期21卷 1373-1380页

作者： YANG Tianyan HUANG Xinxin JIANG Yanlin Fisheries College Zhejiang Ocean UniversityZhoushan 316022China Key Laboratory of Informatization of Habitat Monitoring and Fishery Resource Conservation Research in the East China Sea of Zhejiang Province Zhejiang Ocean UniversityZhoushan 316022China

Bombay duck(Harpadon nehereus)is an economically important species in the estuarine and coastal offshore waters of the Indo-West Pacific.This study aims to reveal the genome-wide genetic characteristics of five populations of H.nehereus from the coastal areas of China by using the genotyping-by-sequencing technique.After strict filtering,32088 high-quality single-nucleotide polymorphism markers were detected and analyzed.The average observed heterozygosity and expected heterozygosity ranged from 0.41651 to 0.56725 and from 0.30998 to 0.45531,respectively,indicating that heterozygosity excess occurred in H.nehereus populations.The nucleotide diversity ranged from 0.63664 to 0.74868,which was larger than those from other marine fishes.No obvious genetic structure was detected among H.nehereus populations,and the genetic variation originated within individuals.Extensive gene exchange caused by longshore currents in the reproductive season might be the primary reason for the weak genetic differentiation.Among various environmental factors,water temperature might be the key element affecting the genetic structure of H.nehereus.Due to the destruction and overfishing of spawning grounds,the fishery resources declined in recent years.This study could serve as a reference for the resource protection and rational utilization of H.nehereus.

关键词： Harpadon nehereus genotyping-by-sequencing population genetics single-nucleotide polymorphisms

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Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study

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World Journal of Psychiatry 2023年第12期13卷 1005-1015页

作者： Yue Li Yi-Xi Wang Xing-Ming Tang Peng Liang Jing-Jie Chen Feng Jiang Qiang Yang Yun-Dan Liang Department of Pathology and Pathophysiology Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina West China School of Public Health and West China Fourth Hospital Sichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND Our previous study reported that the single-nucleotide polymorphism(SNP)rs155979 GC in the promoter region of long-chain non-coding RNA(lncRNA)NONHSAT102891 affects depression susceptibility in a Chinese population.AIM To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population.METHODS This this case-control association study was approved by the Ethics Committee of Chengdu Medical College(approval number:201815).Patient diagnosis was based on DSM-IV criteria.We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology,and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects.The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells.RESULTS Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times[TC/CC vs TT:odds ratio(OR)=1.59,95%confidence interval(CI):1.08-2.35,P=0.019].The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230,and the double SNP CG haplotype was more common in the control group compared to case group,indicating that this haplotype significantly reduced the risk of depression(C/G vs T/A:OR=0.42,95%CI:0.21-0.83,P=0.01).There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group(P>0.05),indicating that the double SNP haplotype has no transcrip-tional activity.CONCLUSION The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

关键词： Long-chain non-coding RNA NONHSAT102891 Depression Susceptibility single-nucleotide polymorphisms Haplotype Transcriptional activity

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Association of MBOAT7 rs641738 polymorphism with hepatocellular carcinoma susceptibility:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2023年第12期15卷 2225-2236页

作者： Min Lai Ya-Lu Qin Qiong-Yu Jin Wen-Jing Chen Jia Hu Department of Gastroenterology the Third Affiliated Hospital of Chengdu Medical College/Chengdu Pidu District People's HospitalChengdu 611730Sichuan ProvinceChina Department of Cardiology the Affiliated Third Hospital of Chengdu Traditional Chinese Medicine University/Chengdu Pidu District Hospital of Traditional Chinese MedicineChengdu 611730Sichuan ProvinceChina

BACKGROUND The MBOAT7 rs641738 single-nucleotide polymorphism(SNP)has been proven to influence various liver diseases,but its association with hepatocellular carcinoma(HCC)susceptibility has been debated.To address this discrepancy,we conducted the current systematic review and meta-analysis.AIM To perform a systematic review and meta-analysis on association of MBOAT7 SNP and HCC susceptibility.METHODS We performed a systematic review in PubMed,Web of Science,Scopus,and EMBASE;applied specific inclusion and exclusion criteria;and extracted the data.Meta-analysis was conducted with the meta package in R.Sensitivity and subgroup analyses were also performed.This meta-analysis was registered in PROSPERO(CRD42023458046).RESULTS Eight studies were included in the systematic review,and 12 cohorts from 6 studies were included in the meta-analysis.Our meta-analysis revealed an association between the MBOAT7 SNP and HCC susceptibility in both the dominant[odds ratio(OR):1.14,95%confidence interval(95%CI):1.02-1.26,P=0.020]and recessive(OR:1.21,95%CI:1.05-1.39,P=0.008)models.Subgroup analysis revealed that stratification of the included patients by geographical origin showed a significant association in Asia(OR:1.20,95%CI:1.03-1.39).CONCLUSION This meta-analysis underscores the contribution of the MBOAT7 rs641738 SNP to hepatocarcinogenesis,especially in Asian populations,which warrants further investigation.

关键词： MBOAT7 single-nucleotide polymorphisms Hepatocellular carcinoma Systematic review Meta-analysis Asian populations

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Genome-wide long non-coding RNA association study on Han Chinese women identifies lncHSAT164 as a novel susceptibility gene for breast cancer

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Chinese Medical Journal 2021年第10期134卷 1138-1145页

作者： Jing-Kai Xu Guo-Zheng Li Zhi Li Wen-Jing Li Run-Sheng Chen Bo Zhang Xue-Jun Zhang Department of Dermatology The First Affiliated Hospital of Anhui Medical UniversityKey Laboratory of DermatologyAnhui Medical UniversityMinistry of EducationHefeiAnhui 230032China Department of Genetics School of Life SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Oncology No.2 HospitalAnhui Medical UniversityHefeiAnhui 230032China Laboratory of Bioinformatics and Noncoding RNA Key Laboratory of RNA BiologyInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China

Background:single-nucleotide polymorphisms(SNPs)-associated genes and long non-coding RNAs(lncRNAs)can contribute to human disease.To comprehensively investigate the contribution of lncRNAs to breast cancer,we performed the first genome-wide lncRNA association study on Han Chinese women.Methods:We designed an lncRNA array containing>800,000 SNPs,which was incorporated into a 96-array plate by Affymetrix(CapitalBio Technology,China).Subsequently,we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals(5634 breast cancer patients and 6308 healthy controls).Additionally,in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene.Results:We identified a novel breast cancer-associated susceptibility SNP,rs11066150(P_(meta)=2.34×10^(-8)),and a previously reported SNP,rs9397435(P_(meta)=4.32×10^(-38)),in Han Chinese women.rs11066150 is located in NONHSAT164009.1(lncHSAT164),which is highly expressed in breast cancer tissues and cell lines.lncHSAT164 overexpression promoted colony formation,whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle.Conclusions:Based on our lncRNA array,we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle.These findings suggest a potential therapeutic target in breast cancer.

关键词： Breast cancer lncHSAT164 single-nucleotide polymorphisms

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A comparison of genetic risk score with family history for estimating prostate cancer risk

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Asian Journal of Andrology 2016年第4期18卷 515-519页

作者： Brian T Helfand Division of Urology NorthShore University HealthSystem University of Chicago Pritzker School of Medicine 2650 Ridge Avenue Evanston IL 60201 USA.

Prostate cancer （PCa） testing is recommended by most authoritative groups for high-risk men including those with a family history of the disease. However, family history information is often limited by patient knowledge and clinician intake, and thus, many men are incorrectly assigned to different risk groups. Alternate methods to assess PCa risk are required. In this review, we discuss how genetic variants, referred to as PCa-risk single-nucleotide polymorphisms, can be used to calculate a genetic risk score （GRS）. GRS assigns a relatively unique value to all men based on the number of PCa-risk SNPs that an individual carries. This GRS value can provide a more precise estimate of a man＇s PCa risk. This is particularly relevant in situations when an individual is unaware of his family history. In addition, GRS has utility and can provide a more precise estimate of risk even among men with a positive family history. It can even distinguish risk among relatives with the same degree of family relationships. Taken together, this review serves to provide support for the clinical utility of GRS as an independent test to provide supplemental information to family history. As such, GRS can serve as a platform to help guide-shared decision-making processes regarding the timing and frequency of PCa testing and biopsies.

关键词： family history genetic risk score prostate cancer single-nucleotide polymorphisms

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ILIF7 Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population： A Case-Control Study

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Chinese Medical Journal 2018年第2期131卷 171-179页

作者： Xiao-Ying Zhang Yu Zuo Chun Li Xin TU Hu-Ji Xu Jian-Ping Guo Zhan-Guo Li Rong Mu Department of Rheumatoiogy and Immunology Peking University People's Hospital and Beijing Key Laboratory for Rheumatism Mechanism and Immune Diaanosis (BZ0135) Beijing 100044 China Department of Rheumatology China-JaPan Friendship Hospital Beijing 100029 China Key Laboratory of Molecular Biophysics of Ministry of Education College of Life Science and Technology Center for Human Benome HesearcnCardio-X Institute Huazhong University of Science and Technology Wuhan Hubei 430000 China Department of Rheumatology and Immunology Shanghai Changzheng Hospital Second Military Medical University Shanghai 200003 China

Background： Interleukin （IL）-37, also called ILl F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis （RA）. This study aimed to investigate the role oflL1F7 gene polymorphism in RA susceptibility in a large cohort of patients. Methods： Five selected single-nucleotide polynaorphisms in IL 1F7 genes （rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270） were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender. Results： Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I （160 patients with RA： 252 healthy controls）. Further validation in Stage II comprised 730 unrelated patients with RA （mean age： 54.9 ± 12.6 years; 81.6% females） and 778 unrelated healthy individuals （mean age： 53.5 ± 15.7 years; 79.5% females）. No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions. Conclusion： 1L1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Hart population.

关键词： ILIF7 Gene lnterleukin-37 Rheumatoid Arthritis single-nucleotide polymorphisms

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