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Aim: Some recent studies on PD have focused on the WNT-2 and TGF-β1 gene loci, but its genetic basis is still not clearly known. In this context, we aimed to evaluate the presence of WNT-2 and TGF-β1 gene expression and genetic similarity between patients with Peyronie’s disease (PD) and comorbidities, especially diabetes mellitus (DM). Methods: Between May 2020 and April 2021, 57 patients diagnosed with PD were included in this cross-sectional study. The presence of comorbidities [Dupuytren’s contracture (DC), DM, hypertension (HT), dyslipidemia, and erectile dysfunction (ED)] was recorded. For genetic analysis, the WNT-2 and TGF-β1 genes were analyzed in the patients’ serum. Results: The mean age was found to be 50.2. 45.6% of the patients had DM, 19.1% had HT, 14% had dyslipidemia, 5.3% had DC, and 40.4% had ED. TGF-β1 gene expression was found to be increased in all patients; WNT-2 gene expression was found to be increased in 80.7%. When subtypes of the TGF-β1 and WNT-2 gene expression were analyzed, 52.6% of patients with WNT-2 gene expression and 95.5% of patients with TGF-β1 gene expression were found to be homozygous, and the others were found to be heterozygous. Patients with DM and PD had significantly higher homozygous WNT-2 gene expression (p=0.03). No significant relationship was found between other comorbidities and these genes. Conclusion: Homozygous WNT-2 gene expression was found to be increased in PD with DM. These data could be used to explain the genetic pathophysiology of PD in diabetic patients.