1. Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, N.C.;
2. Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, N.C.; ; 3. Bioinformatics Services Division, North Carolina Research Campus, Kannapolis, N.C.;
Int J Med Sci. 2014 May 15;11(7):748-53. doi: 10.7150/ijms.8770. eCollection 2014.
Disc degeneration and its associated low back pain are a major health care concern causing disability with a prominent role in this country's medical, social and economic structure. Low back pain is devastating and influences the quality of life for millions. Low back pain lifetime prevalence approximates 80% with an estimated direct cost burden of $86 billion per year. Back pain patients incur higher costs, greater health care utilization, and greater work loss than patients without back pain.
Research was performed following approval of our Institutional Review Board. DNA was isolated, processed and amplified using routine techniques. Amplified DNA was hybridized to Affymetrix Genome-Wide Human SNP Arrays. Quality control and genotyping analysis were performed using Affymetrix Genotyping Console. The Birdseed v2 algorithm was used for genotyping analysis. 2589 SNPs were selected a priori to enter statistical analysis using lotistic regression in SAS.
Our objective was to search for novel single nucleotide polymorphisms (SNPs) associated with disc degeneration. Four SNPs were found to have a significant relationship to disc degeneration; three are novel. Rs165656, a new SNP found to be associated with disc degeneration, was in catechol-O-methyltransferase (COMT), a gene with well-recognized pain involvement, especially in female subjects (p=0.01). Analysis confirmed the previously association between COMT SNP rs4633 and disc degeneration. We also report two novel disc degeneration-related SNPs (rs2095019 and rs470859) located in intergenic regions upstream to thrombospondin 2.
Findings contribute to the challenging field of disc degeneration and pain, and are important in light of the high clinical relevance of low back pain and the need for improved understanding of its fundamental basis.
椎间盘退变及其相关的下腰痛是一个主要的医疗保健问题，导致残疾，在该国的医疗、社会和经济结构中起着重要作用。下腰痛是毁灭性的，影响着数百万人的生活质量。下腰痛的终身患病率接近 80%，估计每年的直接成本负担为 860 亿美元。与没有腰痛的患者相比，腰痛患者的成本更高，医疗利用率更高，工作损失更大。
在获得我们机构审查委员会的批准后，进行了研究。使用常规技术分离、处理和扩增 DNA。扩增的 DNA 与 Affymetrix 全基因组人类 SNP 阵列杂交。使用 Affymetrix 基因分型控制台进行质量控制和基因分型分析。使用 Birdseed v2 算法进行基因分型分析。预先选择了 2589 个 SNP，以便使用 SAS 中的逻辑回归进行统计分析。
我们的目标是寻找与椎间盘退变相关的新的单核苷酸多态性（SNP）。发现有四个 SNP 与椎间盘退变有显著关系；其中三个是新的。与椎间盘退变相关的新 SNP rs165656 位于儿茶酚-O-甲基转移酶（COMT）中，该基因与众所周知的疼痛有关，尤其是在女性中（p=0.01）。分析证实了 COMT SNP rs4633 与椎间盘退变之间的先前关联。我们还报告了两个新的与椎间盘退变相关的 SNP（rs2095019 和 rs470859），位于血小板反应蛋白 2 上游的基因间区域。
这些发现为椎间盘退变和疼痛这一具有挑战性的领域做出了贡献，鉴于下腰痛的高临床相关性以及对其基本基础的深入理解的必要性，这些发现非常重要。
