Dwiki Fitri , Lalu Muhammad Irham , Nanik Sulistyani , Muhammad Ma’ruf , Anisa Nova Puspitaningrum , Wirawan Adikusuma , Maulida Mazaya , Rockie Chong
{"title":"整合基因组学数据库和生物信息学,在多个大洲确定重症肌无力的全基因组变体","authors":"Dwiki Fitri , Lalu Muhammad Irham , Nanik Sulistyani , Muhammad Ma’ruf , Anisa Nova Puspitaningrum , Wirawan Adikusuma , Maulida Mazaya , Rockie Chong","doi":"10.1016/j.bbii.2023.100041","DOIUrl":null,"url":null,"abstract":"<div><p>Autoimmune disease is an immune response that damages the body’s tissues, thereby disrupting the body’s physiological functions. Myasthenia gravis represents one such condition characterized by muscle weakness due to impaired neuromuscular transmission. While it can affect anyone, it tends to be more prevalent among women aged 20–30 and men over 50. This disease, deemed a genetic disorder, typically emerges in old age when antibodies target receptors in the muscles. In this study, we sought to identify the genes that can affect myasthenia gravis by leveraging several databases, including the GWAS Catalog, HaploReg, GTEx portal, and Ensembl. Specifically, our focus was on exploring genomic variants and the expression of the <em>LTA</em> and <em>CTLA4</em> genes. Our findings reveal that two variants (rs2071591 and rs231770) impact <em>LTA</em> expression in both muscle and brain tissue, while affecting <em>CTLA4</em> expression in testicular cell tissue. Subsequently, we assessed the allele frequency of these variants across regional populations, namely African, American, East Asian, European, and Southeast Asian. This study demonstrates that the <em>LTA</em> and <em>CTLA4</em> genes have a higher frequency in African, East Asian, and European populations compared to American and Southeast Asian populations. Consequently, our finding suggests that the latter two populations might have relatively higher susceptibility to the autoimmune disease myasthenia gravis. Therefore, variations in these genes not only offer insights into disease susceptibility, diagnostic or prognostic biomarkers, but also open up avenues for identifying candidate drug targets through genomic-driven drug repurposing.</p></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"5 ","pages":"Article 100041"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949834123000405/pdfft?md5=c52fc63177e914bca4da43eb8c630ef2&pid=1-s2.0-S2949834123000405-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Integration of genomics database and bioinformatics to identify genome-wide variants for myasthenia gravis across multiple continents\",\"authors\":\"Dwiki Fitri , Lalu Muhammad Irham , Nanik Sulistyani , Muhammad Ma’ruf , Anisa Nova Puspitaningrum , Wirawan Adikusuma , Maulida Mazaya , Rockie Chong\",\"doi\":\"10.1016/j.bbii.2023.100041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Autoimmune disease is an immune response that damages the body’s tissues, thereby disrupting the body’s physiological functions. Myasthenia gravis represents one such condition characterized by muscle weakness due to impaired neuromuscular transmission. While it can affect anyone, it tends to be more prevalent among women aged 20–30 and men over 50. This disease, deemed a genetic disorder, typically emerges in old age when antibodies target receptors in the muscles. In this study, we sought to identify the genes that can affect myasthenia gravis by leveraging several databases, including the GWAS Catalog, HaploReg, GTEx portal, and Ensembl. Specifically, our focus was on exploring genomic variants and the expression of the <em>LTA</em> and <em>CTLA4</em> genes. Our findings reveal that two variants (rs2071591 and rs231770) impact <em>LTA</em> expression in both muscle and brain tissue, while affecting <em>CTLA4</em> expression in testicular cell tissue. Subsequently, we assessed the allele frequency of these variants across regional populations, namely African, American, East Asian, European, and Southeast Asian. This study demonstrates that the <em>LTA</em> and <em>CTLA4</em> genes have a higher frequency in African, East Asian, and European populations compared to American and Southeast Asian populations. Consequently, our finding suggests that the latter two populations might have relatively higher susceptibility to the autoimmune disease myasthenia gravis. Therefore, variations in these genes not only offer insights into disease susceptibility, diagnostic or prognostic biomarkers, but also open up avenues for identifying candidate drug targets through genomic-driven drug repurposing.</p></div>\",\"PeriodicalId\":100197,\"journal\":{\"name\":\"Brain Behavior and Immunity Integrative\",\"volume\":\"5 \",\"pages\":\"Article 100041\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2949834123000405/pdfft?md5=c52fc63177e914bca4da43eb8c630ef2&pid=1-s2.0-S2949834123000405-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain Behavior and Immunity Integrative\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2949834123000405\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Behavior and Immunity Integrative","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949834123000405","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Integration of genomics database and bioinformatics to identify genome-wide variants for myasthenia gravis across multiple continents
Autoimmune disease is an immune response that damages the body’s tissues, thereby disrupting the body’s physiological functions. Myasthenia gravis represents one such condition characterized by muscle weakness due to impaired neuromuscular transmission. While it can affect anyone, it tends to be more prevalent among women aged 20–30 and men over 50. This disease, deemed a genetic disorder, typically emerges in old age when antibodies target receptors in the muscles. In this study, we sought to identify the genes that can affect myasthenia gravis by leveraging several databases, including the GWAS Catalog, HaploReg, GTEx portal, and Ensembl. Specifically, our focus was on exploring genomic variants and the expression of the LTA and CTLA4 genes. Our findings reveal that two variants (rs2071591 and rs231770) impact LTA expression in both muscle and brain tissue, while affecting CTLA4 expression in testicular cell tissue. Subsequently, we assessed the allele frequency of these variants across regional populations, namely African, American, East Asian, European, and Southeast Asian. This study demonstrates that the LTA and CTLA4 genes have a higher frequency in African, East Asian, and European populations compared to American and Southeast Asian populations. Consequently, our finding suggests that the latter two populations might have relatively higher susceptibility to the autoimmune disease myasthenia gravis. Therefore, variations in these genes not only offer insights into disease susceptibility, diagnostic or prognostic biomarkers, but also open up avenues for identifying candidate drug targets through genomic-driven drug repurposing.