Department of Orthopaedic Surgery, Tufts University School of Medicine, Boston, MA, USA.
Spine (Phila Pa 1976). 2010 Oct 1;35(21):1909-14. doi: 10.1097/BRS.0b013e3181eea007.
Prospective observational study.
To determine whether polymorphic variations of the guanosine triphosphate (GTP) cyclohydrolase 1 gene (GCH1) are associated with different outcomes in patients undergoing surgical treatment for lumbar degenerative disc disease (DDD).
GCH1, the gene encoding the rate-limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated as a determinant of pain experience in previous animal and human studies. METHODS.: A total of 69 patients undergoing surgical treatment for lumbar DDD were prospectively enrolled. Genomic DNA was extracted from a venous blood sample, and DNA sequence analysis was performed of GCH1. Surgery included 65 instrumented fusions and 4 disc arthroplasty procedures. Patients were observed prospectively for 1 year following surgery. Allelic and genotype frequencies were calculated for each of 14 single nucleotide polymorphisms (SNPs). One-year postoperative Oswestry Disability Index (ODI) scores were compared to preoperative scores and the absolute change in ODI score was used to perform genetic association analyses on the basis of both individual SNP markers as well as commonly observed haplotypes for the entire gene sequence.
Single marker analysis revealed 1 SNP (rs998259; minor allele T) that was significantly associated with improvement in both absolute ODI score (P = 0.030) and Numerical Rating Scale back pain scores (P = 0.033) following surgery. Haplotype analysis identified a common GCH1 haplotype ("CACTTGTTTGAC") with a sample frequency of 12.3%, which was highly associated with improvement in absolute ODI score (P = 0.04). This haplotype frequency reflects the existence of both heterozygous and homozygous individuals in the study population. The presence of 1 unit of this haplotype was associated with an improvement in postoperative ODI score of 15.34 relative to the absence of this haplotype (P = 0.04).
Preliminary results from this pilot genetic study of patients undergoing surgery for DDD suggests that the T allele at rs998259 of GCH1 may be associated with improved outcomes 1 year following surgery.
前瞻性观察研究。
确定鸟苷三磷酸（GTP）环水解酶 1 基因（GCH1）的多态性变异是否与接受腰椎退行性椎间盘疾病（DDD）手术治疗的患者的不同结果相关。
GCH1 是四氢生物蝶呤合成限速酶的编码基因，在之前的动物和人类研究中，它被强烈认为是疼痛体验的决定因素。
共前瞻性纳入 69 例接受腰椎 DDD 手术治疗的患者。从静脉血样中提取基因组 DNA，并对 GCH1 进行 DNA 序列分析。手术包括 65 例器械融合和 4 例椎间盘置换术。术后对患者进行为期 1 年的前瞻性观察。计算了 14 个单核苷酸多态性（SNP）的每个 SNP 的等位基因和基因型频率。比较了术后 1 年的 Oswestry 残疾指数（ODI）评分与术前评分，并根据单个 SNP 标记以及整个基因序列上常见的单倍型，使用 ODI 评分的绝对变化进行遗传关联分析。
单标记分析显示，1 个 SNP（rs998259；次要等位基因 T）与术后 ODI 评分的绝对改善（P=0.030）和数字评分量表腰痛评分（P=0.033）显著相关。单倍型分析确定了一个常见的 GCH1 单倍型（“CACTTGTTTGAC”），样本频率为 12.3%，与 ODI 评分的绝对改善高度相关（P=0.04）。该单倍型频率反映了研究人群中杂合子和纯合子的存在。该单倍型存在 1 个单位与不存在该单倍型相比，术后 ODI 评分改善 15.34（P=0.04）。
来自接受 DDD 手术治疗患者的这项初步遗传研究结果表明，GCH1 中 rs998259 的 T 等位基因可能与术后 1 年的结果改善相关。
