Department of Reproduction and Genetics, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
J Assist Reprod Genet. 2018 Dec;35(12):2223-2231. doi: 10.1007/s10815-018-1316-0. Epub 2018 Sep 18.
The aim of this study was undertaken to investigate the association of 78-kDa glucose-regulated protein (GRP78) gene promoter polymorphisms with risk of asthenozoospermia (AZS) men. In addition, we performed association analysis between GRP78 promoter mutations and serum GRP78 level in asthenozoospermia.
The study population comprised 400 subjects with AZS patients and 400 healthy controls. We assessed GRP78 rs3216733, rs17840761, and rs17840762 polymorphisms by using Snapshot SNP genotyping assays; serum GRP78 level was measured by enzyme-linked immunosorbent assay (ELISA). Semen quality was assessed by computer-assisted semen analysis.
We found that rs3216733 was associated with increased risk of AZS (Gd vs. dd: adjusted OR = 1.42, 95% CI, 1.06-1.93, P = 0.020; Gd/GG vs. dd: adjusted OR = 1.43, 95% CI, 1.08-1.91, P = 0.013; G vs. d adjusted OR = 1.26, 95% CI, 1.03-1.56, P = 0.027). The haplotype analyses showed the frequency of G-C-C haplotype was significantly higher in AZS (P = 0.026). The percentage of progressive motility sperm was lower in the asthenozoospermic men with Gd and Gd/GG genotypes than dd genotype (P = 0.003). Moreover, the serum GRP78 levels were significantly lower in rs3216733 Gd/GG genotypes compared with the dd genotype (P < 0.001).
Our findings suggest that rs3216733 Gd/GG genotypes contribute to poor sperm motility, probably by decreasing the level of GRP78.
本研究旨在探讨 78kDa 葡萄糖调节蛋白（GRP78）基因启动子多态性与弱精子症（AZS）男性发病风险的相关性。此外，我们还分析了 GRP78 启动子突变与 AZS 患者血清 GRP78 水平之间的关联。
研究人群包括 400 例 AZS 患者和 400 例健康对照者。我们采用 Snapshot SNP 基因分型检测技术评估 GRP78 rs3216733、rs17840761 和 rs17840762 多态性；采用酶联免疫吸附试验（ELISA）检测血清 GRP78 水平。通过计算机辅助精液分析评估精液质量。
我们发现 rs3216733 与 AZS 发病风险增加相关（Gd 相比 dd：调整后的 OR=1.42，95%CI，1.06-1.93，P=0.020；Gd/GG 相比 dd：调整后的 OR=1.43，95%CI，1.08-1.91，P=0.013；G 相比 d 调整后的 OR=1.26，95%CI，1.03-1.56，P=0.027）。单体型分析显示，AZS 患者中 G-C-C 单体型的频率明显更高（P=0.026）。与 dd 基因型相比，Gd 和 Gd/GG 基因型的弱精子症患者的前向运动精子比例较低（P=0.003）。此外，与 dd 基因型相比，rs3216733 的 Gd/GG 基因型患者血清 GRP78 水平明显较低（P<0.001）。
我们的研究结果表明，rs3216733 的 Gd/GG 基因型可能通过降低 GRP78 水平导致精子运动能力下降。
