Erin C Peckham-Gregory1, Dharma R Thapa2, Jeremy Martinson3, Priya Duggal4, Sudhir Penugonda5, Jay H Bream6, Po-Yin Chang7, Sugandha Dandekar8, Shen-Chih Chang7, Roger Detels7, Otoniel Martínez-Maza9, Zuo-Feng Zhang7, Shehnaz K Hussain10. 1. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA. Electronic address: Erin.Peckham@bcm.edu. 2. Departments of Obstetrics and Gynecology, and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA. 3. Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, 403 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261, USA. 4. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Room E6539, Baltimore, MD 21205, USA. 5. Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611, USA. 6. Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Room E5624, Baltimore, MD 21205, USA. 7. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA. 8. The UCLA Genotyping and Sequencing Core, Department of Human Genetics, David Geffen School of Medicine, UCLA, CHS 36-125, 650 Charles E Young Drive South, Los Angeles, CA 90095, USA. 9. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA; Departments of Obstetrics and Gynecology, and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA; Jonsson Comprehensive Cancer Center, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA; UCLA AIDS Institute, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA. 10. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA; Department of Medicine and Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd, West Hollywood, CA 90048, USA.
Abstract
BACKGROUND: MicroRNAs, small non-coding RNAs involved in gene regulation, are implicated in lymphomagenesis. We evaluated whether genetic variations in microRNA coding regions, binding sites, or biogenesis genes (collectively referred to as miRNA-SNPs) were associated with risk of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs. METHODS: Twenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV-infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real-time polymerase chain reaction was used to quantify serum microRNA levels. Adjusted odds ratios (ORs) estimated using conditional logistic regression evaluated associations between miRNA-SNPs and AIDS-NHL risk. A semi-Bayes shrinkage approach was employed to reduce likelihood of false-positive associations. Adjusted mean ratios (MR) calculated using linear regression assessed associations between miRNA-SNPs and serum microRNA levels. RESULTS: DDX20 rs197412, a non-synonymous miRNA biogenesis gene SNP, was associated with AIDS-NHL risk (OR=1.34 per minor allele; 95% CI: 1.02-1.75), and higher miRNA-222 serum levels nearing statistical significance (MR=1.21 per minor allele; 95% CI: 0.98-1.49). MiRNA-196a2 rs11614913 was associated with decreased central nervous system (CNS) AIDS-NHL (CT vs. CC OR=0.52; 95% CI: 0.27-0.99). The minor allele of HIF1A rs2057482, which creates a miRNA-196a2 binding site, was associated with systemic AIDS-NHL risk (OR=1.73 per minor allele; 95% CI: 1.12-2.67), and decreased CNS AIDS-NHL risk (OR=0.49 per minor allele; 95% CI: 0.25-0.94). CONCLUSIONS: This study suggests that a few miRNA-SNPs are associated with AIDS-NHL risk and may modulate miRNA expression. These results support a role for miRNA in AIDS-NHL and may highlight pathways to be targeted for risk stratification or therapeutics. Copyright Â
BACKGROUND: MicroRNAs, small non-coding RNAs involved in gene regulation, are implicated in lymphomagenesis. We evaluated whether genetic variations in microRNA coding regions, binding sites, or biogenesis genes (collectively referred to as miRNA-SNPs) were associated with risk of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs. METHODS: Twenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV-infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real-time polymerase chain reaction was used to quantify serum microRNA levels. Adjusted odds ratios (ORs) estimated using conditional logistic regression evaluated associations between miRNA-SNPs and AIDS-NHL risk. A semi-Bayes shrinkage approach was employed to reduce likelihood of false-positive associations. Adjusted mean ratios (MR) calculated using linear regression assessed associations between miRNA-SNPs and serum microRNA levels. RESULTS:DDX20rs197412, a non-synonymous miRNA biogenesis gene SNP, was associated with AIDS-NHL risk (OR=1.34 per minor allele; 95% CI: 1.02-1.75), and higher miRNA-222 serum levels nearing statistical significance (MR=1.21 per minor allele; 95% CI: 0.98-1.49). MiRNA-196a2 rs11614913 was associated with decreased central nervous system (CNS) AIDS-NHL (CT vs. CC OR=0.52; 95% CI: 0.27-0.99). The minor allele of HIF1Ars2057482, which creates a miRNA-196a2 binding site, was associated with systemic AIDS-NHL risk (OR=1.73 per minor allele; 95% CI: 1.12-2.67), and decreased CNS AIDS-NHL risk (OR=0.49 per minor allele; 95% CI: 0.25-0.94). CONCLUSIONS: This study suggests that a few miRNA-SNPs are associated with AIDS-NHL risk and may modulate miRNA expression. These results support a role for miRNA in AIDS-NHL and may highlight pathways to be targeted for risk stratification or therapeutics. Copyright Â
Authors: Lorena Di Lisio; Nerea Martinez; Santiago Montes-Moreno; Miguel Piris-Villaespesa; Margarita Sanchez-Beato; Miguel A Piris Journal: Blood Date: 2012-07-03 Impact factor: 22.113
Authors: Ricardo Ney Oliveira Cobucci; Paulo Henrique Lima; Pollyana Carvalho de Souza; Vanessa Viana Costa; Maria da Conceição de Mesquita Cornetta; José Veríssimo Fernandes; Ana Katherine Gonçalves Journal: J Infect Public Health Date: 2014-10-05 Impact factor: 3.718
Authors: Lindsay M Morton; Jennifer J Turner; James R Cerhan; Martha S Linet; Patrick A Treseler; Christina A Clarke; Andrew Jack; Wendy Cozen; Marc Maynadié; John J Spinelli; Adele Seniori Costantini; Thomas Rüdiger; Aldo Scarpa; Tongzhang Zheng; Dennis D Weisenburger Journal: Blood Date: 2007-03-27 Impact factor: 22.113
Authors: Joel Henrique Ellwanger; Francis Maria Báo Zambra; Rafael Lima Guimarães; José Artur Bogo Chies Journal: Front Immunol Date: 2018-06-14 Impact factor: 7.561