Perera Romain Shanil, Dissanayake Poruwalage Harsha, Senarath Upul, Wijayaratne Lalith Sirimevan, Karunanayake Aranjan Lional, Dissanayake Vajira Harshadeva Weerabaddana
Department of Allied Health Sciences, Faculty of Medicine, University of Colombo, Colombo 8, Sri Lanka.
Department of Anatomy, Faculty of Medical Sciences, University of Sri Jayewardenepura, Gangodawila, Nugegoda, Sri Lanka.
PLoS One. 2017 Jul 24;12(7):e0181580. doi: 10.1371/journal.pone.0181580. eCollection 2017.
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.
椎间盘突出是一种复杂的脊柱疾病，与残疾和高昂的医疗费用相关。腰椎间盘突出与椎间盘退变密切相关。聚集蛋白聚糖代谢途径的候选基因可能与腰椎间盘突出的严重程度相关。
本研究评估了聚集蛋白聚糖代谢途径候选基因的单核苷酸变异（SNV）与慢性机械性下腰痛患者腰椎间盘突出严重程度之间的关联。此外，我们评估了显著SNV的计算机功能分析及其单倍型与腰椎间盘突出严重程度的关联。
对106例患者进行了描述性横断面研究。在T2加权腰椎矢状位MRI扫描上评估椎间盘突出和椎间盘退变的严重程度。在Sequenom MassARRAY iPLEX平台上对聚集蛋白聚糖代谢途径的10个候选基因（ACAN、IL1A、IL1B、IL6、MMP3、ADAMTS4、ADAMTS5、TIMP1、TIMP2和TIMP3）的62个外显子SNV进行基因分型。使用PLINK 1.9软件进行多变量线性回归分析，并对年龄、性别、体重指数和椎间盘退变严重程度进行校正。使用四个在线生物信息学工具（Provean、SIFT、PolyPhen和Mutation Taster）进行计算机功能分析。
平均年龄为52.
42±9.42岁，女性占69.8%。椎间盘突出的平均严重程度为2.81±1.98。ACAN的rs2272023、rs35430524、rs2882676、rs2351491、rs938609、rs3825994、rs1042630、rs698621和rs3817428变异及其单倍型与腰椎间盘突出的严重程度相关。然而，通过计算机功能分析，仅ACAN的rs35430524、rs938609和rs3817428变异被检测为致病性变异。
ACAN的SNV及其单倍型与腰椎间盘突出的严重程度相关。有必要进行功能遗传学研究以确定这些显著SNV在椎间盘突出发病机制中的作用。
