A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo

• Published in: The Prostate 2010-04, Vol.70 (5), p.467-472
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Genetic Predisposition to Disease; Genotype; Humans; Male; MicroRNAs - genetics; Middle Aged; miR-146a; polymorphism; Polymorphism, Genetic; prostate cancer; Prostatic Neoplasms - etiology; Prostatic Neoplasms - genetics; Risk
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.21080

BACKGROUND A G > 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 GG/GC 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. © 2009 Wiley‐Liss, Inc.