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

Genetic variants encoding both low COMT and MTHFR activity are associated with idiopathic scoliosis. The combined impact of and on progression of adolescent idiopathic scoliosis (AIS) is unknown. This study investigated if and low activity variants are associated with AIS progression. Patients with AIS, at least two Cobb angle measurements in adolescence, and those with both low (rs4680 AA) and low (A1298C AC and C677T CT; A1298C AA and C677T TT) activity (Group 1) or those with intermediate or high (rs4680 AG or GG) and (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. Seventy-two patients with AIS diagnosis and required Cobb angle measurements had both and 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). Significantly more patients with both low and low activity variants had progression of AIS than those with intermediate or normal activity variants of and . Further understanding the role of and may inform research regarding treatment modalities.