Dataset Information

Genetic association studies in lumbar disc degeneration: a systematic review.

ABSTRACT:

Objective

Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans.

Methods

A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines.

Results

Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328) and MMP9 (rs17576).

Conclusions

Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

SUBMITTER: Eskola PJ

PROVIDER: S-EPMC3503778 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Genetic association studies in lumbar disc degeneration: a systematic review.

Eskola Pasi J PJ Lemmelä Susanna S Kjaer Per P Solovieva Svetlana S Männikkö Minna M Tommerup Niels N Lind-Thomsen Allan A Husgafvel-Pursiainen Kirsti K Cheung Kenneth M C KM Chan Danny D Samartzis Dino D Karppinen Jaro J

PloS one 20121121 11

<h4>Objective</h4>Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans.<h4>Methods</h4>A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology ...[more]

PMID: 23185509

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Project description:The association between growth differentiation factor 5 (GDF5), single nucleotide polymorphism (SNP) rs143383 and lumbar disc degeneration (LDD) was investigated. A total of 210 patients with LDD (observation group) and 320 patients without lumbar diseases (control group) diagnosed in Shanghai General Hospital of Nanjing Medical University from August 2013 to March 2017 were randomly selected. Then, deoxyribonucleic acid (DNA) was extracted from the blood of each patient, and Taq-man fluorescent quantitative polymerase chain reaction (qPCR) technique was used to detect rs143383 in GFD5 gene. The frequency of different genotypes in observation group and control group was counted, and the associations between different SNP genotypes and the incidence of LDD were analyzed. Good genotyping results were found in both LDD patient group and control group. There were no significant differences in distribution frequency of TT and TC genotypes at site rs143383 between LDD patient group and control group (P>0.05), but the distribution frequency of CC genotype at site rs143383 in LDD patient group had a statistically significant difference from that in control group (P<0.05). In dominant models, odds ratio (OR) of (TC+CC/TT) was 1.195 (P=0.532). In recessive models, OR of (CC/TT+TC) was 4.333 (P=0.028). In co-dominant models, ORs of (TC/TT) and (CC/TT) were 0.967 and 4.43, respectively (P=0.99). The differences in 3 genotypes showed no statistical significance among different pathological grades (Grade I to V) (?2=1.034, P=0.998), and there was no statistically significant difference in T and C (?2=0.012, P=0.999). Pathological grades in dominant models, recessive models and over dominant models were analyzed, and no statistically significant difference was found (P>0.05). In conclusion, CC mutant type at rs143383 in GDF5 gene has a strong association with the incidence of LDD, and a high prevalence risk, but it has no evident correlation with pathological grades.

Project description:Lumbar intervertebral disc degeneration (DD) disease is one of the main risk factors for low back pain and a leading cause of population absenteeism and disability worldwide. Despite a variety of biological studies, lumbar DD is not yet fully understood, partially because there are only few studies that use systematic and integrative approaches. This urges the need for studies that integrate different omics (including genomics and transcriptomics) measured on samples within a single cohort. This protocol describes a disease-oriented Russian disc degeneration study (RuDDS) biobank recruitment and analyses aimed to facilitate further omics studies of lumbar DD integrating genomic, transcriptomic and glycomic data. A total of 1,100 participants aged over 18 with available lumbar MRI scans, medical histories and biological material (whole blood, plasma and intervertebral disc tissue samples from surgically treated patients) will be enrolled during the three-year period from two Russian clinical centers. Whole blood, plasma and disc tissue specimens will be used for genotyping with genome-wide SNP-arrays, glycome profiling and RNA sequencing, respectively. Omics data will be further used for a genome-wide association study of lumbar DD with in silico functional annotation, analysis of plasma glycome and lumbar DD disease interactions and transcriptomic data analysis including an investigation of differential expression patterns associated with lumbar DD disease. Statistical tests applied in each of the analyses will meet the standard criteria specific to the attributed study field. In a long term, the results of the study will expand fundamental knowledge about lumbar DD development and contribute to the elaboration of novel personalized approaches for disease prediction and therapy. Additionally to the lumbar disc degeneration study, a RuDDS cohort could be used for other genetic studies, as it will have unique omics data. Trial registration number NCT04600544.

Dataset Information

Genetic association studies in lumbar disc degeneration: a systematic review.

Objective

Methods

Results

Conclusions

Publications

Genetic association studies in lumbar disc degeneration: a systematic review.

Similar Datasets

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