Dataset Information

Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator.

ABSTRACT: Deep venous thrombosis (DVT) is a common complication of orthopedic surgery. Genetic risk factors and high heritability carried a substantial risk of DVT. In this study, we aimed to investigate the potential association in the Han Chinese population between the polymorphisms of BDKRB2 and KNG1 and DVT after orthopedic surgery (DVTAOS). A total of 3,010 study subjects comprising 892 DVT cases and 2,118 controls were included in the study, and 39 single nucleotide polymorphisms (SNPs) in total (30 for BDKRB2 and 9 for KNG1) were chosen for genotyping. Two SNPs, rs710446 (OR?=?1.27, P?=?0.00016) and rs2069588 (OR?=?1.29, P?=?0.00056), were identified as significantly associated with DVTAOS. After adjusting for BMI, the significance of rs2069588 decreased (P?=?0.0013). Haplotype analyses showed that an LD block containing rs2069588 significantly correlated with the DVTAOS risk. Moreover, bioinformatics analysis indicated that hsa-miR-758-5p and BDKRB2 formed miRNA/SNP target duplexes if the rs2069588 allele was in the T form, suggesting that rs2069588 may alter BDKRB2 expression by affecting hsa-miR-758-5p/single-nucleotide polymorphism target duplexes. Our results demonstrate additional evidence supporting that there is an important role for the KNG1 and BDKRB2 genes in the increased susceptibility of DVTAOS.

SUBMITTER: Wang Q

PROVIDER: S-EPMC6255904 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator.

Wang Qingfeng Q Cheng Guoping G Wang Xiaohui X Wang Dandan D Yang Yanmei Y Chen Ke K Ye Jiumin J Qing Zhong Z

Scientific reports 20181126 1

Deep venous thrombosis (DVT) is a common complication of orthopedic surgery. Genetic risk factors and high heritability carried a substantial risk of DVT. In this study, we aimed to investigate the potential association in the Han Chinese population between the polymorphisms of BDKRB2 and KNG1 and DVT after orthopedic surgery (DVTAOS). A total of 3,010 study subjects comprising 892 DVT cases and 2,118 controls were included in the study, and 39 single nucleotide polymorphisms (SNPs) in total (30 ...[more]

PMID: 30478260

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Project description:BackgroundVenous thromboembolism (VTE) is a significant perioperative risk with many common orthopaedic procedures. Currently, there is no standardized recommendation for the use of VTE prophylaxis during anterior cruciate ligament (ACL) reconstruction. This study sought to evaluate the current prophylactic practices of fellowship-trained sports medicine orthopaedic surgeons in the United States.HypothesisVery few surgeons use perioperative VTE prophylaxis for ACL reconstructive surgery.Study designSurvey.MethodsSurveys were emailed to the alumni networks of 4 large ACGME-accredited sports medicine fellowship programs. Questions were focused on their current use of chemical and nonchemical VTE prophylaxis.ResultsSurveys were completed by 142 surgeons in the United States, yielding a response rate of 32%. Of those who responded, 50.7% stated that they routinely use chemical prophylaxis, with 95.5% of those using aspirin (acetylsalicylic acid [ASA]). There was no standardized dosing protocol, with respondents using ASA 325 mg once (46%) or twice daily (26%) or ASA 81 mg once (18%) or twice (10%) daily. The most common reason for not including chemical prophylaxis within the reconstruction procedure was that it is unnecessary given the low risk of VTE. Physicians also based their prophylaxis regimen more on their own clinical experience than concern for litigation.ConclusionHalf of all sports medicine fellowship-trained surgeons surveyed routinely use chemical VTE prophylaxis after ACL reconstruction, with more than 90% of those using ASA. Of those using ASA, there was no prevailing dosing protocol. For those not using chemical prophylaxis, the most important reason was that it was felt to be unnecessary due to the risks outweighing the benefits. Those who do not regularly use chemical prophylaxis would be willing to, however, if a patient had a personal or family history of clotting disorder or is currently on birth control. Additionally, clinical experience was the primary driver for a current prophylaxis protocol.Clinical relevanceThis survey study evaluating the use of VTE prophylaxis with ACL reconstruction lends clinical insight to the current practice of a large, geographically diverse group of fellowship-trained sports medicine orthopaedic surgeons in the United States.

Project description:Purpose: To explore the possible pathogenesis of venous thromboembolism from the perspective of circRNAs. Methods: The thrombus model of inferior vena cava in SD rats was established by stenosis method. Peripheral blood samples of DVT rats were collected at 1h, 6h,12h and 3d, which were sequenced with Illumina circRNAs and mRNA. The differential circRNAs and mRNA were analyzed by STEM analysis software. Clusters that can reflect the evolution of thrombus were selected for in-depth analysis, and circRNAs and mRNA were screened according to the pathway enrichment analysis of the selected clusters. Real time fluorescent quantitative PCR (qPCR) was used to verify and determine the candidate circRNAs and mRNA. The function of target circRNA was verified in DVT rats. The interacting miRNAs of circRNAs and mRNA were predicted by online database respectively. Candidate miRNAs were identified by integrating the related information of miRNAs and verified by qPCR. Results:The SD rat model of deep venous thrombosis was successfully established by the stenosis method. In model group, there were 736, 3691, 3406 and 2639 circRNAs up-regulated and 944, 327, 318 and 397 circRNAs down-regulated at 1h, 6h, 12h and 3d, respectively. Compared with Sham group, 169, 885, 298 and 500 mRNA were up-regulated and 231, 291,75 and 73 mRNA were down-regulated at 1h, 6h, 12h and 3d in model group, respectively. STEM analysis found that cluster 45 was similar to thrombus development. The pathway related to platelet function was selected in cluster 45, and 10 circrRNAs and 4 interacting mRNAs were selected for qPCR verification by combining the gene in platelet pathway and annotation gene of cluster 45 and mRNA-circRNA interaction network. According to qPCR results and whether ID is found in rat circRNA database (CIRCpedia-V2), CBT15_circR_3235 (ID in circpedia-v2: rno_CIRCpedia_1953) is determined as the target circRNA. In vivo，knockdown of rno_CIRCpedia_1953 attenuates the formation of DVT in rats. The potential target miRNAs of rno_CIRCpedia_1953 and Tuba4a were predicted by using online miRDB and miRWalk databases respectively, and rno-miR-3543, rno-miR-320-5p and rno-miR-26b-3p are preliminarily identified as potential target miRNAs that rno_CIRCpedia_1953 may combine to play the ceRNA mechanism. Conclusions: Animal model of DVT in rats was successfully established by stenosis method. High-throughput sequencing analysis of circRNAs showed that circRNAs participated in the evolution of DVT. According to STEM functional analysis of mRNA sequencing, a target circRNA rno_CIRCpedia _1953 was screened, verified and identified. rno_CIRCpedia_1953 may participate in the development of DVT by acting as miRNA molecular sponge.

Dataset Information

Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator.

Publications

Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator.

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