Medical College, Aga Khan University, Karachi, Pakistan.
Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Int J Clin Pract. 2020 Oct;74(10):e13595. doi: 10.1111/ijcp.13595. Epub 2020 Aug 27.
The objective of this was to demonstrate the association of Inhibin α (INHα) c.-124G>A and INHα-c.-16 C>T polymorphisms with altered sperm parameters in a selected male population of Karachi, Pakistan.
STUDY DESIGN & SETTINGS: In this pilot study, male subjects were stratified on the basis of the WHO criteria for altered sperm parameters; 83 (cases-altered sperm parameters) and 30 (controls-normal sperm parameters) subjects were included for analysis of INHα-c.124G>A polymorphism and 88 (cases) and 38 (controls) were analysed for INHα -c-16 C>T polymorphism. Genotyping of INHα-c.-124G>A and INHα-c.-16 C>T was performed by PCR-RFLP, genotype distribution in Hardy-Weinberg equilibrium was evaluated by binary logistic regression model.
For the c.-124G>A polymorphism in INHα gene, frequency of the three major genotypes in controls was: GG: 80.0%, GA: 20.0% and AA: 0% and in cases was: GG: 59.0%, GA: 30.2% and AA: 10.8%. The GG genotype was significantly associated with male infertility (P < .045, OR = 2.776, 95% CI = 1.025-7.513) while the GA genotype was not significantly associated with infertility (P < .290 OR = 0.580, 95% CI = 0.211-1.593). Frequency of mutant AA genotype was 10.8% in cases (altered sperm parameters) and absent (0%) in normal sperm parameter (controls). The frequencies of three major genotypes CC, CT and TT did not show any significant difference between cases and controls (P > .05).
The results from our study exhibited a significant association of c.-124G>A polymorphism in the INHα gene promoter region with male infertility in the Pakistani population. A significant association of c.-16 C>T polymorphism with male infertility, however, was not observed. Further large-scale studies should be conducted to confirm this association.
本研究旨在展示在巴基斯坦卡拉奇的一个特定男性人群中，抑制素 α (INHα) c.-124G>A 和 INHα-c.-16 C>T 多态性与精子参数改变的关联。
在这项初步研究中，男性受试者根据世界卫生组织（WHO）改变精子参数的标准进行分层；83 名（病例-精子参数改变）和 30 名（对照-精子参数正常）受试者被纳入 INHα-c.124G>A 多态性分析，88 名（病例）和 38 名（对照）受试者被纳入 INHα -c-16 C>T 多态性分析。INHα-c.-124G>A 和 INHα-c.-16 C>T 的基因分型通过 PCR-RFLP 进行，Hardy-Weinberg 平衡的基因型分布通过二元逻辑回归模型进行评估。
在 INHα 基因的 c.-124G>A 多态性中，对照组三种主要基因型的频率为：GG：80.0%、GA：20.0%和 AA：0%，而病例组的频率为：GG：59.0%、GA：30.2%和 AA：10.8%。GG 基因型与男性不育显著相关（P <.045，OR = 2.776，95%CI = 1.025-7.513），而 GA 基因型与不育无显著相关性（P <.290，OR = 0.580，95%CI = 0.211-1.593）。病例组（精子参数改变）中突变 AA 基因型的频率为 10.8%，而正常精子参数（对照组）中则不存在（0%）。病例组和对照组之间三种主要基因型 CC、CT 和 TT 的频率没有显著差异（P >.05）。
本研究结果显示，INHα 基因启动子区 c.-124G>A 多态性与巴基斯坦人群男性不育显著相关。然而，c.-16 C>T 多态性与男性不育的显著关联尚未观察到。应进一步开展大规模研究以证实这一关联。
