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• W2788292278 endingPage "243" @default.
• W2788292278 startingPage "226" @default.
• W2788292278 abstract "Antiphospholipid Syndrome (APS) is an autoimmune multifactorial disorder. Genetics is believed to play a contributory role in the pathogenesis of APS, especially in thrombosis development and pregnancy morbidity. In the last 20 years, extensive research on genetic contribution on APS indicates that APS is a polygenic disorder, where a number of genes are involved in the development of its clinical manifestations. The aim of this systematic review is to evaluate the genetic risk factors in thrombotic primary APS. Additionally, to assess the common molecular functions, biological processes, pathways, interrelations with the gene encoded proteins and RNA-Seq-derived expression patterns over different organs of the associated genes via bioinformatic analyses. Without restricting the year, a systematic search of English articles was conducted (up to 4th September 2017) using Web of Science, PubMed, Scopus, ScienceDirect and Google Scholar databases. Eligible studies were selected based on the inclusion criteria. Two researchers independently extracted the data from the included studies. Quality assessment of the included studies was carried out using a modified New-Castle Ottawa scale (NOS). From an initial search result of 2673 articles, 22 studies were included (1268 primary APS patients and 1649 healthy controls). Twenty-two genes were identified in which 16 were significantly associated with thrombosis in primary APS whereas six genes showed no significant association with thrombosis. Based on the NOS, 14 studies were of high quality while 6 were low quality studies. From the bioinformatic analyses, thrombin-activated receptor activity (q = 6.77 × 10−7), blood coagulation (q = 2.63 × 10−15), formation of fibrin clot (q = 9.76 × 10−10) were the top hit for molecular function, biological process and pathway categories, respectively. With the highest confidence interaction score of 0.900, all of the thrombosis-associated gene encoded proteins of APS were found to be interconnected except for two. Based on the pathway analysis, cumulatively all the genes affect haemostasis [false discovery rate (FDR) = 1.01 × 10−8] and the immune system [FDR = 9.93 × 10−2]. Gene expression analysis from RNA-Seq data revealed that almost all the genes were expressed in 32 different tissues in the human body. According to our systematic review, 16 genes contribute significantly in patients with thrombotic primary APS when compared with controls. Bioinformatic analyses of these genes revealed their molecular interconnectivity in protein levels largely by affecting blood coagulation and immune system. These genes are expressed in 32 different organs and may pose higher risk of developing thrombosis anywhere in the body of primary APS patients." @default.
• W2788292278 created "2018-03-06" @default.
• W2788292278 creator A5008438276 @default.
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• W2788292278 creator A5085478675 @default.
• W2788292278 date "2018-03-01" @default.
• W2788292278 modified "2023-09-24" @default.
• W2788292278 title "Genetic risk factors in thrombotic primary antiphospholipid syndrome: A systematic review with bioinformatic analyses" @default.
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