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This corresponds to an approximately threefold increased risk compared with controls, indicating a potential familial aggregation of the disease ( Polymorphisms in glutathione S-transferase (GST) and nitric oxide synthase (NOS) genes have emerged as focal points in genetic studies of varicocele ( In addition, specific single nucleotide polymorphisms (SNPs) in the nitric oxide synthase 3 (NOS3) gene, such as rs1799983 and rs2070744, show significantly altered distributions in patients with varicocele, suggesting that these variants may contribute to venous dilation by modulating nitric oxide (NO) bioavailability ( UQCRC2 , MIC60 , TOM22 , and LETM1 ( Nevertheless, to date, no specific genetic determinants have been identified that can fully account for the heritability of varicocele or its clinical grading, and the precise roles of these candidate genes within sperm-related signaling pathways remain to be elucidated