Competing targets of microRNA-608 affect anxiety and hypertension.
Bottom Line: We found that changing a single miRNA-target interaction can simultaneously affect multiple other miRNA-target interactions and modify physiological phenotype.Additionally, minor allele heterozygote and homozygote subjects showed reduced cortisol and elevated blood pressure, predicting risk of anxiety and hypertension.We demonstrate that SNPs in miRNA-binding regions could cause expanded downstream effects changing important biological pathways.
Affiliation: The Silberman Institute of Life Sciences and The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, The Edmond Safra Campus, Givat Ram, Jerusalem 91904, Israel.Show MeSH
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Mentions: The HERITAGE Family Study cohort (HEalth, RIsk factors, exercise Training And GEnetics) recruited young, healthy adults, of Caucasian or African-American ethnic origins (36) (see Supplementary Material, Tables S4 and S5 for population characteristics). Genotyping indicated that this cohort includes 63/159 and 13/209 homozygotes or heterozygotes for the minor A-allele in the African-American and Caucasian groups, respectively (Fig. 5A). Separate association analysis for the African-American and Caucasian datasets was then combined using meta-analysis. Volunteers homozygous and heterozygous for the minor A-allele showed sharply reduced serum cortisol levels and higher, albeit non-pathological systolic and diastolic blood pressure compared with homozygotes of the major C-allele (P = 9.77 × 10−8, P = 0.05, P = 0.0031, Fig. 5B–D and Supplementary Material, Fig. S2), in spite of their young age and generally good health (36). Reduced circulating cortisol and elevated blood pressure are known factors predicting increased risks of both anxiety and hypertension-related diseases (39,40). Also, a genome-wide association study in African-Americans reported significant association with hypertension for another SNP, rs78011900, in full linkage disequilibrium with rs17228616 (41).Figure 5.
Affiliation: The Silberman Institute of Life Sciences and The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, The Edmond Safra Campus, Givat Ram, Jerusalem 91904, Israel.