Association of MMP9 and NOS3 Polymorphisms with Distinct Clinical Forms of Juvenile Scleroderma and Characteristics of Humoral Immunity

Juvenile scleroderma (JS), comprising localized (JLSd) and systemic (JSSc) forms, is a rare autoimmune disorder. This study investigated associations of polymorphisms in extracellular matrix (<i>MMP1</i>, <i>MMP9</i>) and vascular homeostasis (<i>NOS3</i>) genes with JS risk and immunological phenotypes. A case-control study involved 215JS patients (194 JLSd, 21 JSSc) and 72 controls. SNPs (<i>MMP1</i> rs1799750, <i>MMP9</i> rs3918242, <i>NOS3</i> rs1799983) were genotyped using real-time PCR followed by minisequencing and mass spectrometric analysis of reaction products. Associations with disease risk, subtypes, and immunological markers were analyzed statistically. <i>The MMP9</i> (rs3918242) CT genotype was significantly associated with JLSd (OR = 2.23, 95% CI: 1.14-4.37, <i>p</i> = 0.022), showing a trend in linear facial forms. The <i>NOS3</i> (rs1799983) GG genotype demonstrated a trend toward association with JSSc (OR = 2.61, 95% CI: 0.92-7.37, <i>p</i> = 0.065). No significant associations were found for rs1799750 <i>MMP1</i> and risk of disease development. The <i>MMP9</i> risk genotype did not correlate with scleroderma-specific autoantibodies, while the <i>NOS3</i> GG genotype was associated with lower serum levels of anti-collagen IV antibodies (<i>p</i> = 0.039). Genetic associations differ for JS subtypes: <i>MMP9</i> with JLSd and <i>NOS3</i> with JSSc. Children with CT polymorphism <i>MMP9</i> (rs3918242) and with <i>NOS3</i> (rs1799983) GG genotype were found to be genetically predisposed for the development of JS.