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

Prostate. 2010 Apr 1;70(5):467-72. doi: 10.1002/pros.21080.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Polymorphism, Genetic*
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / genetics*
  • Risk

Substances

  • MIRN146 microRNA, human
  • MicroRNAs