MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study |
| |
| Institution: | 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;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. 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;8. Jonsson Comprehensive Cancer Center, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA;9. UCLA AIDS Institute, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA;10. Department of Medicine and Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd, West Hollywood, CA 90048, USA;1. Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;2. Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Road, Niao Song District, Kaohsiung, Taiwan;3. Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung, Taiwan;1. Department of Cancer Epidemiology–Oncological Research Center of Santa Catarina (CEPON/SC), Brazil;2. Department of Public Health–Post-graduation Program, Federal University of Santa Catarina (UFSC), Brazil |
| |
| Abstract: | BackgroundMicroRNAs, 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.MethodsTwenty-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.ResultsDDX20 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).ConclusionsThis 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. |
| |
| Keywords: | AIDS-NHL microRNA SNPs microRNA-SNP Lymphoma Epidemiology |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
