A Specific Haplotype of the MMP2 Gene Promoter May Increase the Risk of Developing Cerebral Palsy

<b>Background/Objectives:</b> Hypoxic-ischemic encephalopathy (HIE) is a common neurological outcome of perinatal asphyxia, with cerebral palsy (CP) being the most severe lasting effect. Perinatal brain injury activates the immune system and induces the release of inflammatory mediators. Matrix Metalloproteinases (MMPs) play a crucial role in neuroinflammation and neurodegeneration. This study explored the potential link between <i>MMP2</i> promoter polymorphisms and the development of CP in children with a history of perinatal asphyxia. <b>Methods:</b> We enrolled 212 patients (130 males and 82 females) with documented perinatal asphyxia, who underwent a comprehensive neurological assessment and neuroimaging, including ultrasound and magnetic resonance imaging (MRI). We genotyped the <i>MMP2</i> promoter polymorphisms rs243866, rs243865, and rs243864 using real-time polymerase chain reaction. Haplotype frequencies were calculated using Haploview software. <b>Results:</b> As expected, patients with HIE are more likely to develop CP (<i>p</i> = 0.000). In a study of 104 patients who developed CP, the frequencies of the A (rs243866), T (rs243865), and G alleles (rs243864) were nearly twice as high compared to those without CP (<i>p</i> = 0.008, <i>p</i> = 0.019, and <i>p</i> = 0.008, respectively). Haplotype analysis supported these findings, showing that the ATG haplotype was significantly more common among patients who developed CP (<i>p</i> = 0.004). Additionally, in patients with MRI-confirmed brain damage, the ATG haplotype was more frequently observed (<i>p</i> = 0.019). <b>Conclusions:</b> The ATG haplotype of the <i>MMP2</i> promoter may indicate a risk factor for developing cerebral palsy (CP) in patients who experience perinatal asphyxia and could serve as a potential diagnostic predictor of CP.