Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia
Genome wide association studies (GWAS) have identified several low-penetrance susceptibility alleles in chronic lymphocytic leukemia (CLL). Nevertheless, these studies scarcely study regions that are implicated in non-coding molecules such as microRNAs (miRNAs). Abnormalities in miRNAs, as altered e...
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| description | Genome wide association studies (GWAS) have identified several low-penetrance susceptibility alleles in chronic lymphocytic leukemia (CLL). Nevertheless, these studies scarcely study regions that are implicated in non-coding molecules such as microRNAs (miRNAs). Abnormalities in miRNAs, as altered expression patterns and mutations, have been described in CLL, suggesting their implication in the development of the disease. Genetic variations in miRNAs can affect levels of miRNA expression if present in pre-miRNAs and in miRNA biogenesis genes or alter miRNA function if present in both target mRNA and miRNA sequences. Therefore, the present study aimed to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA processing genes contribute to predisposition for CLL. A total of 91 SNPs in 107 CLL patients and 350 cancer-free controls were successfully analyzed using TaqMan Open Array technology. We found nine statistically significant associations with CLL risk after FDR correction, seven in miRNA processing genes (rs3805500 and rs6877842 in DROSHA, rs1057035 in DICER1, rs17676986 in SND1, rs9611280 in TNRC6B, rs784567 in TRBP and rs11866002 in CNOT1) and two in pre-miRNAs (rs11614913 in miR196a2 and rs2114358 in miR1206). These findings suggest that polymorphisms in genes involved in miRNAs biogenesis pathway as well as in pre-miRNAs contribute to the risk of CLL. Large-scale studies are needed to validate the current findings. |
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Nevertheless, these studies scarcely study regions that are implicated in non-coding molecules such as microRNAs (miRNAs). Abnormalities in miRNAs, as altered expression patterns and mutations, have been described in CLL, suggesting their implication in the development of the disease. Genetic variations in miRNAs can affect levels of miRNA expression if present in pre-miRNAs and in miRNA biogenesis genes or alter miRNA function if present in both target mRNA and miRNA sequences. Therefore, the present study aimed to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA processing genes contribute to predisposition for CLL. A total of 91 SNPs in 107 CLL patients and 350 cancer-free controls were successfully analyzed using TaqMan Open Array technology. We found nine statistically significant associations with CLL risk after FDR correction, seven in miRNA processing genes (rs3805500 and rs6877842 in DROSHA, rs1057035 in DICER1, rs17676986 in SND1, rs9611280 in TNRC6B, rs784567 in TRBP and rs11866002 in CNOT1) and two in pre-miRNAs (rs11614913 in miR196a2 and rs2114358 in miR1206). These findings suggest that polymorphisms in genes involved in miRNAs biogenesis pathway as well as in pre-miRNAs contribute to the risk of CLL. Large-scale studies are needed to validate the current findings.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0118905</identifier><identifier>PMID: 25793711</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abnormalities ; B cells ; Binding sites ; Biosynthesis ; Breast cancer ; Cancer ; Cancer genetics ; Chronic lymphocytic leukemia ; Development and progression ; Evolution ; Gene expression ; Gene sequencing ; Genes ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic variance ; Genetic Variation ; Genetics ; Genome-wide association studies ; Genomes ; Genomics ; Genotyping Techniques ; Haplotypes - genetics ; Humans ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Literature reviews ; Lymphatic leukemia ; Medicine ; MicroRNA ; MicroRNAs ; MicroRNAs - chemistry ; MicroRNAs - genetics ; miRNA ; mRNA ; Mutation ; Nucleic Acid Conformation ; Odontology ; Physical anthropology ; Physiology ; Polymorphism, Single Nucleotide - genetics ; Population ; Risk ; Risk Factors ; RNA Processing, Post-Transcriptional - genetics ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Statistical analysis ; Studies</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0118905-e0118905</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Martin-Guerrero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Martin-Guerrero et al 2015 Martin-Guerrero et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-53a80d3c9cb5a571b2cbb2410947b6c07b647a7f00a676794d936963bb2c8c93</citedby><cites>FETCH-LOGICAL-c692t-53a80d3c9cb5a571b2cbb2410947b6c07b647a7f00a676794d936963bb2c8c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368096/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368096/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25793711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zhang, Baohong</contributor><creatorcontrib>Martin-Guerrero, Idoia</creatorcontrib><creatorcontrib>Gutierrez-Camino, Angela</creatorcontrib><creatorcontrib>Lopez-Lopez, Elixabet</creatorcontrib><creatorcontrib>Bilbao-Aldaiturriaga, Nerea</creatorcontrib><creatorcontrib>Pombar-Gomez, Maria</creatorcontrib><creatorcontrib>Ardanaz, Maite</creatorcontrib><creatorcontrib>Garcia-Orad, Africa</creatorcontrib><title>Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Genome wide association studies (GWAS) have identified several low-penetrance susceptibility alleles in chronic lymphocytic leukemia (CLL). Nevertheless, these studies scarcely study regions that are implicated in non-coding molecules such as microRNAs (miRNAs). Abnormalities in miRNAs, as altered expression patterns and mutations, have been described in CLL, suggesting their implication in the development of the disease. Genetic variations in miRNAs can affect levels of miRNA expression if present in pre-miRNAs and in miRNA biogenesis genes or alter miRNA function if present in both target mRNA and miRNA sequences. Therefore, the present study aimed to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA processing genes contribute to predisposition for CLL. A total of 91 SNPs in 107 CLL patients and 350 cancer-free controls were successfully analyzed using TaqMan Open Array technology. We found nine statistically significant associations with CLL risk after FDR correction, seven in miRNA processing genes (rs3805500 and rs6877842 in DROSHA, rs1057035 in DICER1, rs17676986 in SND1, rs9611280 in TNRC6B, rs784567 in TRBP and rs11866002 in CNOT1) and two in pre-miRNAs (rs11614913 in miR196a2 and rs2114358 in miR1206). These findings suggest that polymorphisms in genes involved in miRNAs biogenesis pathway as well as in pre-miRNAs contribute to the risk of CLL. Large-scale studies are needed to validate the current findings.</description><subject>Abnormalities</subject><subject>B cells</subject><subject>Binding sites</subject><subject>Biosynthesis</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Chronic lymphocytic leukemia</subject><subject>Development and progression</subject><subject>Evolution</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic variance</subject><subject>Genetic Variation</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotyping Techniques</subject><subject>Haplotypes - genetics</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Literature reviews</subject><subject>Lymphatic leukemia</subject><subject>Medicine</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - chemistry</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>mRNA</subject><subject>Mutation</subject><subject>Nucleic Acid Conformation</subject><subject>Odontology</subject><subject>Physical anthropology</subject><subject>Physiology</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Population</subject><subject>Risk</subject><subject>Risk Factors</subject><subject>RNA Processing, Post-Transcriptional - genetics</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical 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variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia</title><author>Martin-Guerrero, Idoia ; Gutierrez-Camino, Angela ; Lopez-Lopez, Elixabet ; Bilbao-Aldaiturriaga, Nerea ; Pombar-Gomez, Maria ; Ardanaz, Maite ; Garcia-Orad, Africa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-53a80d3c9cb5a571b2cbb2410947b6c07b647a7f00a676794d936963bb2c8c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Abnormalities</topic><topic>B cells</topic><topic>Binding sites</topic><topic>Biosynthesis</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer genetics</topic><topic>Chronic lymphocytic leukemia</topic><topic>Development and progression</topic><topic>Evolution</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic variance</topic><topic>Genetic Variation</topic><topic>Genetics</topic><topic>Genome-wide association studies</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotyping Techniques</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</topic><topic>Literature reviews</topic><topic>Lymphatic leukemia</topic><topic>Medicine</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - chemistry</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>mRNA</topic><topic>Mutation</topic><topic>Nucleic Acid Conformation</topic><topic>Odontology</topic><topic>Physical anthropology</topic><topic>Physiology</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Population</topic><topic>Risk</topic><topic>Risk Factors</topic><topic>RNA Processing, Post-Transcriptional - 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One</addtitle><date>2015-03-20</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0118905</spage><epage>e0118905</epage><pages>e0118905-e0118905</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Genome wide association studies (GWAS) have identified several low-penetrance susceptibility alleles in chronic lymphocytic leukemia (CLL). Nevertheless, these studies scarcely study regions that are implicated in non-coding molecules such as microRNAs (miRNAs). Abnormalities in miRNAs, as altered expression patterns and mutations, have been described in CLL, suggesting their implication in the development of the disease. Genetic variations in miRNAs can affect levels of miRNA expression if present in pre-miRNAs and in miRNA biogenesis genes or alter miRNA function if present in both target mRNA and miRNA sequences. Therefore, the present study aimed to evaluate whether polymorphisms in pre-miRNAs, and/or miRNA processing genes contribute to predisposition for CLL. A total of 91 SNPs in 107 CLL patients and 350 cancer-free controls were successfully analyzed using TaqMan Open Array technology. We found nine statistically significant associations with CLL risk after FDR correction, seven in miRNA processing genes (rs3805500 and rs6877842 in DROSHA, rs1057035 in DICER1, rs17676986 in SND1, rs9611280 in TNRC6B, rs784567 in TRBP and rs11866002 in CNOT1) and two in pre-miRNAs (rs11614913 in miR196a2 and rs2114358 in miR1206). These findings suggest that polymorphisms in genes involved in miRNAs biogenesis pathway as well as in pre-miRNAs contribute to the risk of CLL. Large-scale studies are needed to validate the current findings.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25793711</pmid><doi>10.1371/journal.pone.0118905</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-03, Vol.10 (3), p.e0118905-e0118905 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abnormalities B cells Binding sites Biosynthesis Breast cancer Cancer Cancer genetics Chronic lymphocytic leukemia Development and progression Evolution Gene expression Gene sequencing Genes Genetic aspects Genetic diversity Genetic Predisposition to Disease Genetic variance Genetic Variation Genetics Genome-wide association studies Genomes Genomics Genotyping Techniques Haplotypes - genetics Humans Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - genetics Literature reviews Lymphatic leukemia Medicine MicroRNA MicroRNAs MicroRNAs - chemistry MicroRNAs - genetics miRNA mRNA Mutation Nucleic Acid Conformation Odontology Physical anthropology Physiology Polymorphism, Single Nucleotide - genetics Population Risk Risk Factors RNA Processing, Post-Transcriptional - genetics Single nucleotide polymorphisms Single-nucleotide polymorphism Statistical analysis Studies |
| title | Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T17%3A41%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20variants%20in%20miRNA%20processing%20genes%20and%20pre-miRNAs%20are%20associated%20with%20the%20risk%20of%20chronic%20lymphocytic%20leukemia&rft.jtitle=PloS%20one&rft.au=Martin-Guerrero,%20Idoia&rft.date=2015-03-20&rft.volume=10&rft.issue=3&rft.spage=e0118905&rft.epage=e0118905&rft.pages=e0118905-e0118905&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0118905&rft_dat=%3Cgale_plos_%3EA423859378%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1664930478&rft_id=info:pmid/25793711&rft_galeid=A423859378&rft_doaj_id=oai_doaj_org_article_bdfb59a0506242ccb0670b1ef66b29fe&rfr_iscdi=true |