Genetic Association Studies in Lumbar Disk Degeneration: A Systematic Review

Abstract

Introduction Low back pain (LBP) is one of the most disabling conditions associated with substantial socioeconomic and health care consequences. LBP is associated with lumbar disk degeneration, which is mainly accounted for genetic predisposition. The objective was to perform a systematic review to assess the level of evidence of polymorphisms associated with lumbar disk degeneration as defined on magnetic resonance imaging (MRI) in humans, evaluate study methods and findings to facilitate further efforts, and assess the clinical relevance of current information. Materials and Methods We performed a systematic literature search on MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database, and The Human Genome Epidemiology Network for information published between 1990 and 2011 addressing genes and lumbar disk degeneration. Two investigators independently identified studies to determine inclusion and study selection, and to perform data extraction, which consisted of study characteristics, population structure, phenotypes, genotyping details, possible biases, and significance of the association results. Results Total 52 studies were included for review. Total 48 studies reported at least one positive association between a genetic marker and lumbar disk degeneration. Level of evidence for the genetic associations was analyzed according to The HuGENet Working Group guidelines. Phenotype definition of lumbar disk degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with weak level of evidence. Due to the heterogeneity between studies, meta-analyses could not be justified. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328), and MMP9(rs17576). Conclusion Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Phenotype definitions of disk degeneration were inconsistent in studies, which impeded meta-analysis. Clear definition of lumbar disk degeneration and large population-based cohorts are needed. An international consortium is needed to establish standardization of genetic association studies in relation to disk degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared