Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia

Idoia Martin-Guerrero; Angela Gutierrez-Camino; Elixabet Lopez-Lopez; Nerea Bilbao-Aldaiturriaga; Maria Pombar-Gomez; Maite Ardanaz; Africa Garcia-Orad

doi:10.1371/journal.pone.0118905

Genetic variants in miRNA processing genes and pre-miRNAs are associated with the risk of chronic lymphocytic leukemia

PLoS One. 2015 Mar 20;10(3):e0118905. doi: 10.1371/journal.pone.0118905. eCollection 2015.

Authors

Idoia Martin-Guerrero¹, Angela Gutierrez-Camino¹, Elixabet Lopez-Lopez¹, Nerea Bilbao-Aldaiturriaga¹, Maria Pombar-Gomez¹, Maite Ardanaz², Africa Garcia-Orad³

Affiliations

¹ Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country, UPV/EHU, Bilbao, Spain.
² Hospital Txagorritxu, Vitoria, Spain.
³ Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Odontology, University of the Basque Country, UPV/EHU, Bilbao, Spain; BioCruces Health Research Institute, UPV/EHU, Leioa, Spain.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genetic Predisposition to Disease*
Genetic Variation*
Genotyping Techniques
Haplotypes / genetics
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
MicroRNAs / chemistry
MicroRNAs / genetics*
Nucleic Acid Conformation
Polymorphism, Single Nucleotide / genetics
RNA Processing, Post-Transcriptional / genetics*
Risk Factors

Substances

MicroRNAs

Grants and funding

This work was supported by the Basque Government (IT661-13), UPV/EHU (UFI11/35), Saiotek (S-PE13UN079) and RTICC (RD12/0036/0060, RD12/0036/0036). AGC was supported by a predoctoral grant from the Basque Government through the grant “Programa de Formación de Personal Investigador no doctor del Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco”. ELL was supported by a postdoctoral grant from the Basque Government through the grant “Programa Posdoctoral, de Perfeccionamiento de Personal Investigador Doctor del Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.