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A novel catechol-O-methyltransferase variant associated with human disc degeneration.

ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

SUBMITTER: Gruber HE

PROVIDER: S-EPMC4045795 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A novel catechol-O-methyltransferase variant associated with human disc degeneration.

Gruber Helen E HE Sha Wei W Brouwer Cory R CR Steuerwald Nury N Hoelscher Gretchen L GL Hanley Edward N EN

International journal of medical sciences 20140515 7

<h4>Background</h4>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 ...[more]

PMID: 24904231

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Project description:Background contextDisc degeneration (DD) is a multifaceted chronic process that alters the structure and function of the intervertebral discs and can lead to painful conditions. The pathophysiology of degeneration is not well understood, but previous studies suggest that certain genetic polymorphisms may be important contributing factors leading to an increased risk of DD.PurposeTo review the genetic factors in DD with a focus on polymorphisms and their putative role in the pathophysiology of degeneration. Elucidating the genetic components that are associated with degeneration could provide insights into the mechanism of the process. Furthermore, defining these relationships and eventually using them in a clinical setting may allow an identification and early intervention for those who are at a high risk for painful DD.Study designLiterature review.MethodsThis literature review focused on the studies concerning genetic polymorphisms and their associations with DD.ResultsGenetic polymorphisms in 20 genes have been analyzed in association with DD, including vitamin D receptor, growth differentiation factor 5 (GDF5), aggrecan, collagen Types I, IX, and XI, fibronectin, hyaluronan and proteoglycan link protein 1 (HAPLN1), thrombospondin, cartilage intermediate layer protein (CILP), asporin, MMP1, 2, and 3, parkinson protein 2, E3 ubiquitin protein ligase (PARK2), proteosome subunit ? type 9 (PSMB9), tissue inhibitor of metalloproteinase (TIMP), cyclooxygenase-2 (COX2), and IL1?, IL1?, and IL6. Each genetic polymorphism codes for a protein that has a functional role in the pathogenesis of DD.ConclusionsThere are known associations between several genetic polymorphisms and DD. Of the 20 genes analyzed, polymorphisms in vitamin D receptor, aggrecan, Type IX collagen, asporin, MMP3, IL1, and IL6 show the most promise as functional variants. Genetic studies are crucial for understanding the mechanism of the degeneration. This genetic information could eventually be used as a predictive model for determining a patient's risk for symptomatic DD.

Project description:BackgroundThis study aimed to develop a classification system for lumbar disc degeneration using routine magnetic resonance images (MRIs) that is easily applicable and unaffected by existing classifications' limitations, and to compare its reliability, reproducibility, and discriminative power to the widely used Pfirrmann classification.MethodsFive features were graded. This new classification system has eight grades, with at least one of these five features altering each grade. The T2-weighted sagittal images were acquired using a rapid spin-echo sequence with a repetition time of 2680 to 4900 milliseconds, an echo time of 100 to 109 milliseconds, and an echo train length of 17. Slice thick was 4 mm and the display field of view was 32 × 32 cm. The new classification system used five features: signal intensity, disc height, disc boundary regularity, and nucleus annulus separation. Increased signal intensity, decreased height, decreased regularity, and decreased nucleus-annulus separation indicated degeneration. Four raters classified 400 discs from 80 patients using the Pfirrmann and Novel systems. Statistical analyses were conducted to investigate reliability and correlation.ResultsThe overall ICC and kappa values were found to be higher in the novel classification. (0.988 indicating excellent agreement for ICC and 0.76/0.94 indicating good-very good agreement for kappa). The Kendall tau c value, which shows the correlation between the two classifications and indicates the validity of the new classification, was 0.872, which is very strong. Through the use of cross-tabulations, the discriminatory power of the two newly added classification criteria was determined.ConclusionsThis study demonstrates the intra-rater and inter-rater reliability of an easy-to-use, discriminative novel morphometric MRI based classification system for lumbar disc degeneration. The differentiation of grades based on five distinct criteria may generate novel hypotheses regarding treatment selection and response monitoring, as well as new insights into the study of disc degeneration.

Dataset Information

A novel catechol-O-methyltransferase variant associated with human disc degeneration.

Publications

A novel catechol-O-methyltransferase variant associated with human disc degeneration.

Similar Datasets

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