Objective: To study the relationship of the single nucleotide polymorphisms (SNP) rs34349826 (c.104 A>G) and rs6521 (c.114 C>G) of the luteinizing hormone beta-subunit (LHB) gene with male infertility in Chinese men.
Methods: This case-control study included 405 males with primary infertility (the infertility group) and 424 normal fertile men (the control group), the former again divided into subgroups of oligospermia, severe oligozoospermia and azoospermia according to the sperm concentration. Clinical data were collected from all the subjects and genomic DNA obtained from their peripheral blood for genotyping rs34349826 and rs6521 of the LHB gene by Sequence MassArray. We analyzed the correlation of male infertility with the SNPs of the two loci using the logistic regression model as well as its association with their haplotype combination with the SHEsis online software.
Results: There were statistically significant differences between the control and infertility groups in the semen volume (［3.51 ± 1.36］ vs ［3.74 ± 1.71］ ml, P <0.05), sperm concentration (［79.21 ± 61.60］ vs ［27.37 ± 30.80］ ×10⁶/ml, P <0.01), percentage of progressively motile sperm (［39.40 ± 9.64］ % vs ［11.90 ± 14.72］ %, P <0.01), and levels of serum luteinizing hormone (LH) (［3.29 ± 1.39］ vs ［6.25 ± 4.83］ IU/L, P <0.01) and follicle-stimulating hormone (FSH) (［4.56 ± 2.31］ vs ［15.64 ± 17.03］ IU/L, P <0.01). Logistic regression analysis revealed no correlation between male infertility and the genotypes of the rs34349826 and rs6521 loci of the LHB gene, and similar results were found in the subgroups of the infertile males. SHEsis analysis on the haplotypes of the rs34349826 and rs6521 loci showed the GG genotype combination to be a protective factor against male infertility.
Conclusions: The rs34349826 and rs6521 loci of the LHB gene were not related to male infertility, which can be further confirmed by larger-sample studies. The GG genotype combination is a protective factor against male infertility.
目的： 研究黄体生成素β亚基(LHB）基因的rs34349826（c.104 A>G）和rs6521（c.114 C>G）位点单核苷酸多态性（SNP）与男性不育之间的相关性。 方法： 采用病例-对照的试验方法，纳入就诊于南京总医院的男性原发性不育患者405例（病例组）和有正常生育史的健康男性424例（对照组）。同时，按照WHO《人类精液检查与处理实验室手册》第5版，根据精子浓度将病例组分为少精子症组、严重少精子症组和无精子症组。收集所有 研究对象的临床基本资料，并采集外周血提取基因组DNA，，使用Sequence MassArray技术进行LHB基因rs34349826和rs6521位点基因型的检测，建立Logistic回归模型分析两位点多态性与男性不育间的关联；并使用SHEsis在线软件对两位点单倍型分析其单倍型组合与男性不育的关系。结果： 病例组与对照组在精液量［（3.74±1.71）ml vs（3.51±1.36）ml］、精子浓度［（27.37±30.80）×10⁶/ml vs（79.21±61.60）×10⁶/ml］、前向运动精子百分率［（11.90±14.72）% vs（39.40±9.64）%］、LH［（6.25±4.83）IU /L vs（3.29±1.39）IU/L］和FSH［（15.64±17.03）IU/L vs（4.56±2.31）IU /L］差异显著（P<0.05），经logistic回归分析，发现LHB rs34349826位点和LHB rs6521位点的各基因型与男性不育无相关性，亚组分析也无相关性。而SHEsis软件对LHB rs34349826和rs6521两个位点单倍型分析，发现在病例组对照组中，GG型基因组合是男性不育的保护因素；亚组-对照组也发现类似结论。结论： LHB基因rs34349826和rs6521位点的多态性与男性不育均无相关性，但后期可以通过扩大样本量进一步证实。而单倍型分析，GG型基因组合是男性不育的保护因素。.
Keywords: male infertility; rs34349826; rs6521; single nucleotide polymorphism; luteinizing hormone beta-subunit (LHB) gene.