Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Prostate. 2010 Apr 1;70(5):467-72. doi: 10.1002/pros.21080.
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.
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.
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.
The natural genetic variation in pre-miR-146a affects the amount of mature miR-146a, contributes to the genetic predisposition to CaP.
miR-146a 前体序列中的 G>C 多态性（rs2910164）导致其茎区的 G:U 对变为 C:U 错配。为了探讨 rs2910164 是否在前列腺癌（CaP）中发挥作用，我们分析了 miR-146a 多态性与 CaP 风险的关联以及不同基因型在南方汉族人群 CaP 组织中的 miR-146a 表达情况。
251 例 CaP 患者和 280 例对照者纳入癌症关联研究，15 例 CaP 组织样本用于通过实时定量逆转录 PCR 检测 miRNA 前体的表达。
我们发现，与携带 GG/GC 基因型的个体相比，携带 CC 纯合子的个体患 CaP 的风险降低了 0.65 倍（95%CI=0.43-0.99，P=0.03），C 等位基因比 G 等位基因更易患 CaP（OR=0.73，95%CI=0.57-0.94，P=0.01）。此外，hsa-miR-146a 的定量显示，与携带 GG/GC 基因型的个体相比，C 变体的纯合子携带者的成熟 miR-146a 水平显著降低。
pre-miR-146a 的天然遗传变异影响成熟 miR-146a 的数量，有助于 CaP 的遗传易感性。
