Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain.
Disc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation.This study evaluated the...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5524386?pdf=render |
| _version_ | 1828750063759785984 |
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| author | Romain Shanil Perera Poruwalage Harsha Dissanayake Upul Senarath Lalith Sirimevan Wijayaratne Aranjan Lional Karunanayake Vajira Harshadeva Weerabaddana Dissanayake |
| author_facet | Romain Shanil Perera Poruwalage Harsha Dissanayake Upul Senarath Lalith Sirimevan Wijayaratne Aranjan Lional Karunanayake Vajira Harshadeva Weerabaddana Dissanayake |
| author_sort | Romain Shanil Perera |
| collection | DOAJ |
| description | Disc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation.This study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation.A descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis.Mean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis.SNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation. |
| first_indexed | 2024-12-10T20:32:28Z |
| format | Article |
| id | doaj.art-773adabb9dc04699bd7a311af15806c9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T20:32:28Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-773adabb9dc04699bd7a311af15806c92022-12-22T01:34:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018158010.1371/journal.pone.0181580Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain.Romain Shanil PereraPoruwalage Harsha DissanayakeUpul SenarathLalith Sirimevan WijayaratneAranjan Lional KarunanayakeVajira Harshadeva Weerabaddana DissanayakeDisc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation.This study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation.A descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis.Mean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis.SNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.http://europepmc.org/articles/PMC5524386?pdf=render |
| spellingShingle | Romain Shanil Perera Poruwalage Harsha Dissanayake Upul Senarath Lalith Sirimevan Wijayaratne Aranjan Lional Karunanayake Vajira Harshadeva Weerabaddana Dissanayake Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain. PLoS ONE |
| title | Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain. |
| title_full | Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain. |
| title_fullStr | Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain. |
| title_full_unstemmed | Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain. |
| title_short | Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain. |
| title_sort | variants of acan are associated with severity of lumbar disc herniation in patients with chronic low back pain |
| url | http://europepmc.org/articles/PMC5524386?pdf=render |
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