Dataset Information

Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes.

ABSTRACT:

Introduction

Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes.

Objectives

The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed.

Methods

A descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster.

Results

Mean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool.

Conclusions

SNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent.

SUBMITTER: Perera RS

PROVIDER: S-EPMC5231268 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes.

Perera Romain Shanil RS Dissanayake Poruwalage Harsha PH Senarath Upul U Wijayaratne Lalith Sirimevan LS Karunanayake Aranjan Lional AL Dissanayake Vajira Harshadeva Weerabaddana VH

PloS one 20170112 1

<h4>Introduction</h4>Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes.<h4>Objectives</h4>The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional an ...[more]

PMID: 28081267

Similar Datasets

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.

Dataset Information

Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes.

Introduction

Objectives

Methods

Results

Conclusions

Publications

Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes.

Similar Datasets

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