Department of Pharmacy, Tehran University of Medical Sciences, P.O. Box: 64155-65117, Tehran, Iran.
Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
BMC Med Genomics. 2024 May 10;17(1):128. doi: 10.1186/s12920-024-01897-5.
The parallel rise in obesity and male infertility in modern societies necessitates the identification of susceptibility genes underlying these interconnected health issues. In our study, we conducted a comprehensive search in the OMIM database to identify genes commonly associated with male infertility and obesity. Subsequently, we performed an insilico analysis using the REVEL algorithm to detect pathogenic single nucleotide polymorphisms (SNPs) in the coding region of these candidate genes. To validate our findings in vivo, we conducted a comprehensive analysis of SNPs and gene expression of candidate genes in 200 obese infertile subjects and 240 obese fertile individuals using ARMS-PCR. Additionally, we analyzed 20 fertile and 22 infertile obese individuals using Realtime-qPCR. By removing duplicated queries, we obtained 197 obesity-related genes and 102 male infertility-related genes from the OMIM database. Interestingly, the APOB gene was found in common between the two datasets. REVEL identified the rs13306194 variant as potentially pathogenic with a calculated score of 0.524. The study identified a significant association between the AA (P value = 0.001) genotype and A allele (P value = 0.003) of the APOB rs13306194 variant and infertility in obese men. APOB expression levels were significantly lower in obese infertile men compared to obese fertile controls (p < 0.01). Moreover, the AA genotype of rs13306194 APOB was associated with a significant decrease in APOB gene expression in obese infertile men (p = 0.05). There is a significant association between the Waist-to-Hip Ratio (WHR) and LH with infertility in the obese infertile group. These results are likely to contribute to a better understanding of the causes of male infertility and its association with obesity.
在现代社会，肥胖症和男性不育症的平行上升使得确定这些相互关联的健康问题的易感基因成为必要。在我们的研究中，我们在 OMIM 数据库中进行了全面搜索，以确定与男性不育和肥胖相关的常见基因。随后，我们使用 REVEL 算法对这些候选基因的编码区进行了计算机分析，以检测致病的单核苷酸多态性（SNP）。为了在体内验证我们的发现，我们使用 ARMS-PCR 对 200 名肥胖不育患者和 240 名肥胖生育能力正常的个体的候选基因的 SNP 和基因表达进行了全面分析。此外，我们还使用 Realtime-qPCR 分析了 20 名生育能力正常和 22 名不育肥胖个体。通过去除重复查询，我们从 OMIM 数据库中获得了 197 个肥胖相关基因和 102 个男性不育相关基因。有趣的是，两个数据集之间存在 APOB 基因。REVEL 将 rs13306194 变体鉴定为潜在致病变体，其计算得分为 0.524。研究发现，APOB rs13306194 变体的 AA（P 值=0.001）基因型和 A 等位基因（P 值=0.003）与肥胖男性不育之间存在显著相关性。与肥胖生育能力正常的对照组相比，肥胖不育男性的 APOB 表达水平明显降低（p<0.01）。此外，APOB rs13306194 APOB 的 AA 基因型与肥胖不育男性 APOB 基因表达显著降低相关（p=0.05）。肥胖不育组中，腰臀比（WHR）和 LH 与不育之间存在显著相关性。这些结果可能有助于更好地理解男性不育的原因及其与肥胖的关系。
