MicroRNAs in the miR-17 and miR-15 families are downregulated in chronic kidney disease with hypertension.

TitleMicroRNAs in the miR-17 and miR-15 families are downregulated in chronic kidney disease with hypertension.
Publication TypeJournal Article
Year of Publication2017
AuthorsNandakumar, P, Tin, A, Grove, ML, Ma, J, Boerwinkle, E, Coresh, J, Chakravarti, A
JournalPLoS One
Date Published2017
KeywordsDown-Regulation, Female, Gene Expression Profiling, Gene Ontology, Gene Regulatory Networks, Humans, Hypertension, Male, MicroRNAs, Middle Aged, Renal Insufficiency, Chronic, RNA, Messenger, Sequence Analysis, RNA

BACKGROUND: In older adults (aged 70-74 years), African-Americans have 4-fold higher risk of developing hypertension-attributed end-stage renal disease (ESRD) than European-Americans. A hypothesized mechanism linking hypertension and progressive chronic kidney disease (CKD) is the innate immune response and inflammation. Persons with CKD are also more susceptible to infection. Gene expression in peripheral blood can provide a view of the innate immune activation profile. We aimed to identify differentially expressed genes, microRNAs, and pathways in peripheral blood between cases with CKD and high blood pressure under hypertension treatment versus controls without CKD and with controlled blood pressure in African Americans.

METHODS: Case and control pairs (N = 15x2) were selected from those without diabetes and were matched for age, sex, body mass index, APOL1 risk allele count, and hypertension medication use. High blood pressure under hypertension treatment was defined as hypertension medication use and systolic blood pressure (SBP) ≥ 145 mmHg. CKD was defined as estimated glomerular filtration rate (eGFR)

RESULTS: Of 347 miRNAs included in the analysis, 14 were significantly associated with case status (Benjamini-Hochberg adjusted p-value [BH p]

CONCLUSION: We have identified 14 differentially expressed miRNAs in the peripheral blood of CKD cases with high blood pressure under hypertension treatment as compared to appropriate controls. Most of the significant miRNAs were downregulated and have critical roles in immune cell functions. Future studies are needed to replicate our findings and determine whether the downregulation of these miRNAs in immune cells may influence CKD progression or complications.

Alternate JournalPLoS One
PubMed ID28771472
PubMed Central IDPMC5542606
Grant ListR21 DK112087 / DK / NIDDK NIH HHS / United States
T32 GM007814 / GM / NIGMS NIH HHS / United States