Wright Jessica, Kekic Adrijana, Vincent Ann, Lacanlale Jana Kay, Melik Razan El, Matey Eric, Morningstar Mark
Mayo Clinic, Rochester, MN, USA.
Mayo Clinic, Phoenix, AZ, USA.
J Genomics. 2025 Jan 1;13:1-5. doi: 10.7150/jgen.104110. eCollection 2025.
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.
编码低儿茶酚-O-甲基转移酶（COMT）和亚甲基四氢叶酸还原酶（MTHFR）活性的基因变异与特发性脊柱侧凸相关。二者对青少年特发性脊柱侧凸（AIS）进展的联合影响尚不清楚。本研究调查了COMT和MTHFR低活性变异是否与AIS进展相关。纳入了患有AIS、在青春期至少有两次Cobb角测量值的患者，以及同时具有低COMT（rs4680 AA）和低MTHFR（A1298C AC和C677T CT；A1298C AA和C677T TT）活性的患者（第1组）或具有中等或高COMT（rs4680 AG或GG）和MTHFR（A1298C AA和C677T CT；A1298C AC和C677T CC；A1298C AA和C677T CC）活性的患者（第2组）。排除患有神经肌肉性或综合征性脊柱侧凸的患者。主要结局是脊柱侧凸的进展，定义为从诊断到骨骼成熟期间Cobb角增加至少20度或进行脊柱手术。通过卡方检验分析主要结局。72例诊断为AIS且需要进行Cobb角测量的患者，其COMT和MTHFR结果符合第1组（n = 41）或第2组（n = 31）的标准。关于主要结局，第1组中78.0%（32/41）的患者病情进展，而第2组中为48.4%（15/31）（p = 0.009）。与具有中等或正常COMT和MTHFR活性变异的患者相比，同时具有低COMT和低MTHFR活性变异的患者中AIS进展的患者明显更多。进一步了解COMT和MTHFR的作用可能为治疗方式的研究提供信息。
