Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome
Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome
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DOI：
10.1111/and.12077
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发表时间：
2014-04-01
期刊：
影响因子：
2.4
通讯作者：
Sengoku, K.
中科院分区：
文献类型：
--
作者：
Miyamoto, T.;Koh, E.;Sengoku, K.
遗传机制被认为是某些男性不育症的原因。最近，通过对人类睾丸组织的表达谱芯片分析，已经鉴定了包括人类LRWD 1在内的10个与人类精子发生有关的新基因。人LRWD 1蛋白介导染色质中的起点识别复合物，这对于G1中复制前复合物组装和G1后细胞中染色质组织的启动至关重要。Lrwd 1基因在小鼠睾丸中的表达是特异性的。因此，我们推测LRWD 1基因突变或多态性与男性不育，尤其是无精子症有关。为了研究LRWD 1基因缺陷是否与SCOS和减数分裂阻滞（MA）引起的无精子症相关，分别对100例和30例日本患者的编码区进行直接测序，进行突变分析。对患有SCOS和MA的患者以及100名健康对照男性进行统计分析。未发现LRWD 1突变，但在患者中可检测到3个编码单核苷酸多态性（SNP 1-SNP 3）。SCOS组SNP 1和SNP 2基因型和等位基因频率均显著高于对照组（P
Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, ten novel genes involved in human spermatogenesis, including human LRWD1, have been identified by expression microarray analysis of human testictissue. The human LRWD1 protein mediates the origin recognition complex in chromatin, which is critical for the initiation of pre-replication complex assembly in G1 and chromatin organization in post-G1 cells. The Lrwd1 gene expression is specific to the testis in mice. Therefore, we hypothesized that mutation or polymorphisms of LRWD1 participate in male infertility, especially azoospermia. To investigate whether LRWD1 gene defects are associated with azoospermia caused by SCOS and meiotic arrest (MA), mutational analysis was performed in 100 and 30 Japanese patients by direct sequencing of the coding regions, respectively. Statistical analysis was performed for patients with SCOS and MA and in 100 healthy control men. No mutations were found in LRWD1; however, three coding single-nucleotide polymorphisms (SNP1-SNP3) could be detected in the patients. The genotype and allele frequencies in SNP1 and SNP2 were notably higher in the SCOS group than in the control group (P