Impact of MMP1, MMP2, and MMP3 Gene Variations on Susceptibility to Peyronie’s Disease and Clinical Progression

The aim of this study was to determine the association between matrix metalloproteinase (MMP1, MMP2, and MMP3) gene variations and susceptibility to Peyronie’s disease, and to investigate their effects on disease progression. This cross-sectional case–control study included a total of 182 individuals—91 patients with Peyronie’s disease and 91 healthy controls. Peripheral venous blood samples (5 mL) were collected, and genomic DNA was isolated using standard spin-column extraction kits. The promoter regions of MMP1, MMP2, and MMP3 were amplified via polymerase chain reaction (PCR), and genotyping was performed using restriction fragment length polymorphism (RFLP) assays with specific restriction endonucleases. All genotyping procedures were conducted in a blinded fashion. Hardy–Weinberg equilibrium analysis (HWE), binary logistic regression with rigorous multiplicity adjustments (Bonferroni-adjusted p-values), and non-parametric Kruskal–Wallis/Mann–Whitney tests with Dunn–Bonferroni post hoc comparisons were utilized. The frequency of the 2G allele for MMP1 (−1607 1G/2G) was significantly higher in the patient group (0.4830) compared to the control group (0.2360; p < 0.05). Similarly, significant differences in allele frequencies were observed for MMP2 (−735 C/T) and MMP3 (−1171 5A/6A) between the cohorts (p < 0.05). HWE analysis confirmed that all investigated variations were in equilibrium in both groups (all p > 0.05). Logistic regression analysis showed that the MMP1 1G/1G genotype was associated with lower odds of Peyronie’s disease (OR: 0.250, p < 0.001), while the 1G/2G (OR: 2.032, p = 0.023) and 2G/2G (OR: 3.509, p = 0.005) genotypes were significantly associated with increased odds. Temporally, carriers of the MMP1 2G/2G genotype presented predominantly in the acute phase, exhibiting a significantly shorter median symptom duration (6.00 months, IQR: 3.00–9.00) compared to 1G/1G carriers (12.00 months, IQR: 5.25–36.00; p = 0.016, adj p = 0.048). For MMP2 (−735 C/T), the CC genotype was associated with higher odds of Peyronie’s disease (OR: 3.049, p < 0.001), while the TT genotype was associated with lower odds (OR: 0.278, p = 0.002). Furthermore, penile plaques were detected in 90% of patients with the CC genotype (p < 0.001). Patients with the CC genotype presented with a median symptom duration of 6.00 months (IQR: 3.00–12.00), whereas TT carriers exhibited a significantly longer duration (24.00 months, IQR: 4.00–48.00; p = 0.002, adj p = 0.006). Regarding MMP3 (−1171 5A/6A), the 5A/5A (OR: 3.930, p = 0.002) and 5A/6A (OR: 2.050, p = 0.022) genotypes were significantly associated with increased odds of the disease, while the 6A/6A genotype showed an inverse association (OR: 0.226, p < 0.001). Patients carrying the 5A allele presented characteristically in the acute phase, with a median symptom duration of 6.00 months (5A/5A) or 4.00 months (5A/6A), which was significantly extended to a median of 24.00 months (IQR: 7.50–54.00) in the 6A/6A genotype (p < 0.001, adj p < 0.001). The findings indicate robust statistical associations between the MMP1 2G, MMP2 C, and MMP3 5A alleles and increased susceptibility to Peyronie’s disease, as well as distinct correlations with compressed symptom durations, acute-phase characteristics, and plaque presence. Because this study relied on peripheral blood DNA genotyping without direct tissue expression quantification in a cross-sectional design, these genetic variations reflect strong exploratory associations rather than direct causal evidence. These markers highlight significant prognostic potential that warrants validation in larger, prospective, longitudinal cohorts.