Association of catechol-O-methyltransferase genetic variants with outcome in patients undergoing surgical treatment for lumbar degenerative disc disease

作者：Dai Feng; Belfer Inna^*; Schwartz Carolyn E; Banco Robert; Martha Julia F; Tighioughart Hocine; Tromanhauser Scott G; Jenis Louis G; Kim David H

来源：Spine Journal, 2010, 10(11): 949-957.

DOI：10.1016/j.spinee.2010.07.387

• COMT
• Chronic pain
• Degenerative disc disease
• Surgical outcome
• Genetic variation

BACKGROUND CONTEXT: Surgical treatment for lumbar degenerative disc disease (DDD) has been associated with highly variable results in terms of postoperative pain relief and functional improvement. Many experts believe that DDD should be considered a chronic pain disorder as opposed to a degenerative disease. Genetic variation of the catechol-O-methyltransferase (COMT) gene has been associated with variation in human pain sensitivity and response to analgesics in previous studies.
PURPOSE: To determine whether genetic variation of COMT is associated with clinical outcome after surgical treatment for DDD.
STUDY DESIGN: Prospective genetic association study.
PATIENT SAMPLE: Sixty-nine patients undergoing surgical treatment for lumbar DDD. Diagnosis was based on documentation of chronic disabling low back pain (LBP) present for a minimum of 6 months and unresponsive to supervised nonoperative treatment, including activity modification, medication, physical therapy, and/or injection therapy. Plain radiographs and magnetic resonance imaging revealed intervertebral disc desiccation, tears, and/or collapse without focal herniation, nerve root compression, stenosis. spondylolisthesis, spondylolysis, or alternative diagnoses.
OUTCOME MEASURES: Oswestry Disability Index (ODI) and visual analog score (VAS) for LBP.
METHODS: Surgical treatment included 65 instrumented fusions and four disc arthroplasty procedures. All patients completed preoperative and 1-year postoperative ODI questionnaires. DNA was extracted from a sample of venous blood, and genotype analysis was performed for five common COMT single nucleotide polymorphisms (SNPs). Potential genetic association between these COMT SNPs and the primary outcome variable, 1-year change in ODI, was investigated using both single-marker and haplotype association analyses. Association with VAS scores for LBP was analyzed as a secondary outcome variable.
RESULTS: Single-marker analysis revealed that the COMT SNP rs4633 was significantly associated with greater improvement in ODI score 1 year after surgery (p=.03), with individuals homozygous for the less common "T" allele demonstrating the largest improvement in ODI. Haplotype analysis of four COMT SNPs, rs6269, rs4633, rs4818, and rs4680, also identified a common haplotype "ATCA" (haplotype frequency of 39.3% in the study population) associated with greater improvement in ODI (p=.046). The greatest mean improvement in ODI was observed in patients homozygous for the "ATCA" COMT haplotype. A nonsignificant trend was observed between SNP rs4633 and greater improvement in VAS score for LBP.
CONCLUSIONS: This is the first study to report an association between surgical treatment success in DDD patients and genetic variation in the putative pain sensitivity gene COMT. These findings require replication in other DDD populations but suggest that genetic testing for pain-relevant genetic markers such as COMT may provide useful clinical information in terms of predicting outcome after surgery for patients diagnosed with DDD.

• 出版日期2010-11