与睾丸微石症患者的睾丸生殖细胞肿瘤和睾丸发育不良相关的基因。
Genes associated with testicular germ cell tumors and testicular dysgenesis in patients with testicular microlithiasis.
机构信息
Russian Medical Academy of Postgraduate Education, Moscow 123995, Russia.
N. N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
出版信息
Asian J Androl. 2018 Nov-Dec;20(6):593-599. doi: 10.4103/aja.aja_54_18.
Testicular microlithiasis (TM) is one of the symptoms of testicular dysgenesis syndrome (TDS). TM is particularly interesting as an informative marker of testicular germ cell tumors (TGCTs). KIT ligand gene (KITLG), BCL2 antagonist/killer 1 (BAK1), and sprouty RTK signaling antagonist 4 (SPRY4) genes are associated with a high risk of TGCTs, whereas bone morphogenetic protein 7 gene (BMP7), transforming growth factor beta receptor 3 gene (TGFBR3), and homeobox D cluster genes (HOXD) are related to TDS. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, we investigated allele and genotype frequencies for KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), BAK1 (rs210138), BMP7 (rs388286), TGFBR3 (rs12082710), and HOXD (rs17198432) in 142 TGCT patients, 137 TM patients, and 153 fertile men (control group). We found significant differences in the KITLG GG_rs995030 genotype in TM (P = 0.01) and TGCT patients (P = 0.0005) compared with the control. We also revealed strong associations between KITLG_rs1508595 and TM (G allele, P = 0.003; GG genotype, P = 0.01) and between KITLG_rs1508595 and TGCTs (G allele, P = 0.0001; GG genotype, P = 0.0007). Moreover, there was a significant difference in BMP7_rs388286 between the TGCT group and the control (T allele, P = 0.00004; TT genotype, P = 0.00006) and between the TM group and the control (T allele, P = 0.04). HOXD also demonstrated a strong association with TGCTs (rs17198432 A allele, P = 0.0001; AA genotype, P = 0.001). Furthermore, significant differences were found between the TGCT group and the control in the BAK1_rs210138 G allele (P = 0.03) and the GG genotype (P = 0.01). KITLG and BMP7 genes, associated with the development of TGCTs, may also be related to TM. In summary, the KITLG GG_rs995030, GG_rs1508595, BMP7 TT_rs388286, HOXD AA_rs17198432, and BAK1 GG_rs210138 genotypes were associated with a high risk of TGCT development.
睾丸微石症 (TM) 是睾丸发育不良综合征 (TDS) 的症状之一。TM 作为睾丸生殖细胞肿瘤 (TGCT) 的信息标志物特别有趣。KIT 配体基因 (KITLG)、BCL2 拮抗剂/杀伤 1 (BAK1) 和芽生 RTK 信号拮抗剂 4 (SPRY4) 基因与 TGCT 的高风险相关，而骨形态发生蛋白 7 基因 (BMP7)、转化生长因子β受体 3 基因 (TGFBR3) 和同源盒 D 簇基因 (HOXD) 与 TDS 相关。使用聚合酶链反应-限制性片段长度多态性 (PCR-RFLP) 分析，我们研究了 KITLG(rs995030、rs1508595)、SPRY4(rs4624820、rs6897876)、BAK1(rs210138)、BMP7(rs388286)、TGFBR3(rs12082710)和 HOXD(rs17198432) 在 142 例 TGCT 患者、137 例 TM 患者和 153 名生育男性 (对照组) 中的等位基因和基因型频率。我们发现 TM (P = 0.01) 和 TGCT 患者 (P = 0.0005) 中 KITLG GG_rs995030 基因型存在显著差异与对照组相比。我们还揭示了 KITLG_rs1508595 与 TM (G 等位基因，P = 0.003；GG 基因型，P = 0.01) 和 KITLG_rs1508595 与 TGCT 之间的强关联 (G 等位基因，P = 0.0001；GG 基因型，P = 0.0007)。此外，TGCT 组与对照组之间 (T 等位基因，P = 0.00004；TT 基因型，P = 0.00006) 和 TM 组与对照组之间 (T 等位基因，P = 0.04) 在 BMP7_rs388286 方面存在显著差异。HOXD 也与 TGCT 具有很强的关联 (rs17198432 A 等位基因，P = 0.0001；AA 基因型，P = 0.001)。此外，在 TGCT 组和对照组之间发现 BAK1_rs210138 G 等位基因 (P = 0.03) 和 GG 基因型 (P = 0.01) 存在显著差异。与 TGCT 发展相关的 KITLG 和 BMP7 基因也可能与 TM 有关。总之，KITLG GG_rs995030、GG_rs1508595、BMP7 TT_rs388286、HOXD AA_rs17198432 和 BAK1 GG_rs210138 基因型与 TGCT 发展的高风险相关。
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