Department of Gynecology and Obstetrics, Reproductive Medical Center, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Cardiovascular Medicine, Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluation, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Dec 12;14:1279058. doi: 10.3389/fendo.2023.1279058. eCollection 2023.
To assess the causal effect of type 2 diabetes mellitus (T2DM) on male infertility (MI) and erectile dysfunction (ED) by Mendelian randomization (MR) analysis.
Data for T2DM, MI, and ED were obtained from genome-wide association studies (GWAS) involving 298, 957, 73, 479, and 223, 805 Europeans, respectively. We performed univariate MR analysis using MR Egger, Weighted median (WM) and Inverse variance weighted (IVW) methods to assess causal effects among the three. Through the Genotype Tissue Expression (GTEx) database, single-nucleotide polymorphisms (SNPs) that affect the expression levels of T2DM-related genes were located using expression quantitative trait loci (eQTL).
MR analysis showed a significant causal relationship between T2DM and ED (WM, OR: 1.180, 95%CI: 1.010-1.378, = 0.037; IVW, OR: 1.190, 95%CI: 1.084-1.300, < 0.001). There is also a significant causal relationship between T2DM and MI (MR Egger, OR: 0.549, 95%CI: 0.317-0.952, = 0.037; WM, OR: 0.593, 95%CI: 0.400, = 0.010; IVW, OR: 0.767, 95%CI: 0.600-0.980, = 0.034). ED may not cause MI ( > 0.05). We also found that rs6585827 corresponding to the PLEKHA1 gene associated with T2DM is an eQTL variant affecting the expression of this gene.
T2DM has a direct causal effect on ED and MI. The level of PLEKHA1 expression suppressed by rs6585827 is potentially associated with a lower risk of T2DM.
通过孟德尔随机化（MR）分析评估 2 型糖尿病（T2DM）对男性不育（MI）和勃起功能障碍（ED）的因果影响。
T2DM、MI 和 ED 数据分别来自涉及 298957、73479、223805 名欧洲人的全基因组关联研究（GWAS）。我们使用 MR Egger、加权中位数（WM）和逆方差加权（IVW）方法进行单变量 MR 分析，以评估这三种疾病之间的因果关系。通过基因型组织表达（GTEx）数据库，使用表达数量性状基因座（eQTL）定位影响 T2DM 相关基因表达水平的单核苷酸多态性（SNP）。
MR 分析显示 T2DM 与 ED 之间存在显著的因果关系（WM，OR：1.180，95%CI：1.010-1.378， = 0.037；IVW，OR：1.190，95%CI：1.084-1.300， < 0.001）。T2DM 与 MI 之间也存在显著的因果关系（MR Egger，OR：0.549，95%CI：0.317-0.952， = 0.037；WM，OR：0.593，95%CI：0.400， = 0.010；IVW，OR：0.767，95%CI：0.600-0.980， = 0.034）。ED 可能不会导致 MI（>0.05）。我们还发现，与 T2DM 相关的 rs6585827 对应于 PLEKHA1 基因，是影响该基因表达的 eQTL 变异。
T2DM 对 ED 和 MI 有直接的因果关系。rs6585827 抑制 PLEKHA1 表达的水平可能与 T2DM 风险降低有关。
