COMT and MTHFR Genetic Variants Combined Effects on Adolescent Idiopathic Scoliosis Progression

<b>Purpose:</b> Genetic variants encoding both low COMT and MTHFR activity are associated with idiopathic scoliosis. The combined impact of <i>COMT</i> and <i>MTHFR</i> on progression of adolescent idiopathic scoliosis (AIS) is unknown. This study investigated if <i>COMT</i> and <i>MTHFR</i> low activity variants are associated with AIS progression. <b>Methods:</b> Patients with AIS, at least two Cobb angle measurements in adolescence, and those with both low <i>COMT</i> (rs4680 AA) and low <i>MTHFR</i> (A1298C AC and C677T CT; A1298C AA and C677T TT) activity (Group 1) or those with intermediate or high <i>COMT</i> (rs4680 AG or GG) and <i>MTHFR</i> (A1298C AA and C677T CT; A1298C AC and C677T CC; A1298C AA and C677T CC) activity (Group 2) were included. Those with neuromuscular or syndromic scoliosis were excluded. The primary outcome was progression of scoliosis, defined as a Cobb angle increase of at least 20 degrees or spinal surgery between the time of diagnosis and skeletal maturity. The primary outcome was analyzed via a Chi-square test. <b>Results:</b> Seventy-two patients with AIS diagnosis and required Cobb angle measurements had both <i>COMT</i> and <i>MTHFR</i> results that met criteria for Group 1 (n=41) or Group 2 (n=31). Regarding the primary outcome, 78.0% (32/41) in Group 1 progressed versus 48.4% (15/31) of patients in Group 2 (p=0.009). <b>Conclusion:</b> Significantly more patients with both low <i>COMT</i> and low <i>MTHFR</i> activity variants had progression of AIS than those with intermediate or normal activity variants of <i>COMT</i> and <i>MTHFR</i>. Further understanding the role of <i>COMT</i> and <i>MTHFR</i> may inform research regarding treatment modalities.