A Functional Polymorphism in Pre-miR-146a Gene Is Associated With Prostate Cancer Risk and Mature miR-146a Expression In Vivo

作者:Xu, Bin; Feng, Ning-Han; Li, Peng-Chao; Tao, Jun; Wu, Deyao; Zhang, Zheng-Dong; Tong, Na; Wang, Jin-Feng; Song, Ning-Hong; Zhang, Wei; Hua, Li-Xin*; Wu, Hong-Fei
来源:Prostate, 2010, 70(5): 467-472.
DOI:10.1002/pros.21080

摘要

BACKGROUND. AG > C polymorphism (rs2910164) which is located in the sequence of miR-146a precursor, results in a change from a G:U pair to a C:U mismatch in its stem region. To explore whether rs2910164 plays any role in prostate cancer (CaP), we analyzed the association between miR-146a polymorphism and risk of CaP and the expression of miR-146a with different genotypes in CaP tissues in southern Chinese Han population. @@@ MATERIALS AND METHODS. Two hundred fifty-one CaP and 280 control subjects were included in the cancer association study, and 15 CaP tissue samples were used to test the expression of the miRNA precursors by real-time quantitative reverse transcription PCR. @@@ RESULTS. We found that subjects carrying CC homozygotes had a 0.65-fold reduced risk (95% CI = 0.43-0.99) than those carrying GG/GC genotypes (P = 0.03), and the C allele displayed a lower prevalence of CaP compared with the G allele (OR = 0.73, 95% CI=0.57-0.94, P=0.01). Moreover, hsa-miR-146a quantification showed that homozygous carriers of the C-variant had significantly decreased miRNA levels compared to the carriers of the CC/CC genotype. @@@ CONCLUSIONS. The natural genetic variation in pre-miR-146a affects the amount of mature miR-146a, contributes to the genetic predisposition to CaP. Prostate 70: 467-472, 2010.