Correlation of EYS polymorphisms with lumbar disc herniation risk among Han Chinese population.

BACKGROUND: Lumbar disc herniation (LDH) is a common spinal disease in clinical practice. Once lumbar disc herniation occurs, it seriously reduces patient's quality of life. The EYS (eyes shut homolog) was discovered in recent years and it may be related to lumbar disc herniation. So we conducted a case-control study to explore the relationship between EYS polymorphism and lumbar disc herniation risk. METHODS: We selected 5 single-nucleotide polymorphisms (SNPs) of EYS gene in a case-control study with 508 cases and 508 healthy controls to evaluate the relatedness by using genetic model, haplotype, and stratification analysis. RESULTS: We found that the minor alleles of rs62413038 (OR = 1.21, 95%CI: 1.01-1.43, p = .036) and rs9450607 (OR = 1.26, 95% CI: 1.05-1.53, p = .016) were associated with an increased risk of lumbar disc herniation in the allelic model analysis. In the genotypic model analysis, rs62413038 displayed a significantly increased risk of lumbar disc herniation in log-additive models (OR = 1.20, 95% CI: 1.01-1.43, p = .039). While the rs9450607 was also obviously associated with an increased lumbar disc herniation risk in recessive (OR = 1.98, 95% CI: 1.24-3.13, p = .004) and log-additive models (OR = 1.27, 95% CI: 1.05-1.55, p = .014). In addition, in the haplotype analyses of the SNPs, we found that the "CGGA" haplotype of rs1482456, rs9342097, rs9450607, and rs7757884 was associated with lumbar disc herniation. (OR = 0.52, 95% CI: 0.30-0.89, p = .017). CONCLUSION: These results suggest that EYS polymorphism may be associated with lumbar disc herniation among Han Chinese population. It also opens up a new exploration direction for the etiology of lumbar disc herniation.

Association between GDF5 rs143383 genetic polymorphism and musculoskeletal degenerative diseases susceptibility: a meta-analysis.

BACKGROUND: Several studies have assessed the association between GDF5 rs143383 polymorphism and the susceptibility of musculoskeletal degenerative diseases, such as intervertebral disc degeneration (IDD) and osteoarthritis (OA), but the results are inconsistent. The aim of our study was to evaluate the association between them comprehensively. METHODS: A systematical search was conducted on PubMed, Scopus, Web of Science (WOS), Embase, and the Cochrane Library databases updated to April 20, 2018. Eligible studies about polymorphisms in GDF5 gene and risk of IDD or OA were included. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized. RESULTS: Fifteen studies with a total of 5915 cases and 12,252 controls were finally included in our study. Meta-analysis of GDF5 rs143383 polymorphism was statistically associated with increased risk of musculoskeletal degenerative diseases under each genetic model (allele model: OR = 1.32, 95% CI 1.19-1.48, P = 0.000; homozygote model: OR = 1.80, 95%CI 1.49-2.16, P = 0.000; heterozygote model: OR = 1.37, 95%CI 1.21-1.55, P = 0.000; dominant model: OR = 1.56, 95%CI 1.39-1.75, P = 0.000; recessive model: OR = 1.39, 95%CI 1.20-1.60, P = 0.000). Stratified analyses based on disease type showed a significant association between the GDF5 rs143383 polymorphism and increased risk of IDD and OA under all genetic models studied. When stratified with ethnicity, pooled outcomes revealed that this polymorphism was significantly related with increased risk of musculoskeletal degenerative diseases in both Asian and Caucasian populations under all genetic models studied. CONCLUSIONS: The present study suggested that GDF5 rs143383 polymorphism was significantly associated with susceptibility to musculoskeletal degenerative diseases.

A preliminary association study of fat mass and obesity associated gene polymorphisms and degenerative disc disease in a Chinese Han population.

OBJECTIVE: To assess whether polymorphisms of the fat mass and obesity associated gene (FTO) are associated with the presence and severity of degenerative disc disease (DDD) in a Chinese Han population. METHODS: In this case-control study, patients with DDD and controls matched for age, sex and body mass index were genotyped for six single nucleotide polymorphisms (SNPs) of FTO. Disease severity was measured using the Japanese Orthopaedic Association score. Allelic, genotypic and genotype-phenotype association analyses were performed. RESULTS: A total of 80 patients with DDD and 80 controls were studied. All six SNPs were in Hardy-Weinberg equilibrium. The frequencies of allele G and genotype G/G of the SNP rs11076008 were significantly associated with DDD after Bonferroni correction. No associations were shown between the SNPs studied and sex or disease severity. CONCLUSION: The SNP rs11076008 of FTO may play an important role in the development of DDD in a Chinese Han population. The G/G genotype and/or G allele may be a risk factor for DDD. These results suggest that FTO is a DDD predisposition gene and may support a close relationship between obesity and DDD.

Prevalence and sex difference of lumbar disc space narrowing in elderly chinese men and women: osteoporotic fractures in men (Hong Kong) and osteoporotic fractures in women (Hong Kong) studies.

OBJECTIVE: Osteoporotic Fractures in Men (Hong Kong) and Osteoporotic Fractures in Women (Hong Kong) represent the first large-scale prospective population-based studies on bone health in elderly (age≥65 years) Chinese men (n=2,000) and women (n=2,000). We undertook the current study to investigate the prevalence of lumbar disc space narrowing in these subjects, and to identify the potential relationship between disc space narrowing and sex, bone mineral density (BMD), and other demographic and clinical data. METHODS: On lumbar lateral radiographs, L1/L2-L4/L5 disc space was classified into 4 categories: 0=normal; 1=mild narrowing; 2=moderate narrowing; 3=severe narrowing. We compared demographic and clinical data between subjects with and those without total disc space narrowing scores≥3. RESULTS: Disc space narrowing was more common in elderly women than in elderly men. The mean±SD disc space narrowing score for the 4 discs was 2.71±2.21 for men and 3.08±2.50 for women (P<0.0001). For the 3 age groups of 65-69 years, 70-79 years, and ≥80 years, the average disc space narrowing score increased with increasing age in both men and women, and to a greater degree in women than in men. The average disc space narrowing score differences between women and men were 0.12, 0.40, and 0.90, respectively, in the 3 age groups. For both men and women, a disc space narrowing score≥3 was associated with older age, higher spine and hip BMD, low back pain, and restricted leg mobility. CONCLUSION: The prevalence and severity of disc space narrowing are higher in elderly women than in elderly men. With increasing age, disc space narrowing progresses at a greater rate in women than in men. A disc space narrowing score≥3 is associated with higher spine and hip BMD.

Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects.

OBJECTIVE: Lumbar disc degeneration (LDD) is an important cause of low back pain, which is a common and costly problem. LDD is characterised by disc space narrowing and osteophyte growth at the circumference of the disc. To date, the agnostic search of the genome by genome-wide association (GWA) to identify common variants associated with LDD has not been fruitful. This study is the first GWA meta-analysis of LDD. METHODS: We have developed a continuous trait based on disc space narrowing and osteophytes growth which is measurable on all forms of imaging (plain radiograph, CT scan and MRI) and performed a meta-analysis of five cohorts of Northern European extraction each having GWA data imputed to HapMap V.2. RESULTS: This study of 4600 individuals identified four single nucleotide polymorphisms with p<5×10(-8), the threshold set for genome-wide significance. We identified a variant in the PARK2 gene (p=2.8×10(-8)) associated with LDD. Differential methylation at one CpG island of the PARK2 promoter was observed in a small subset of subjects (ß=8.74×10(-4), p=0.006). CONCLUSIONS: LDD accounts for a considerable proportion of low back pain and the pathogenesis of LDD is poorly understood. This work provides evidence of association of the PARK2 gene and suggests that methylation of the PARK2 promoter may influence degeneration of the intervertebral disc. This gene has not previously been considered a candidate in LDD and further functional work is needed on this hitherto unsuspected pathway.

Association of FAS and FAS ligand polymorphisms with the susceptibility and severity of lumbar disc degeneration in Chinese Han population.

CONTEXT: Apoptosis is involved in the mechanism of lumbar disc degeneration (LDD). OBJECTIVE: We aim to determine whether the polymorphisms of FAS and FASL are associated with the presence and severity of LDD. METHODS: A total of 348 patients with LDD and 215 healthy controls were genotyped. RESULTS: Patients with LDD showed higher frequency of-1377GA and AA, as well as-844CT and TT genotypes than normal controls. These genotypes were found to be associated with the risk of higher grades of LDD. CONCLUSION: The polymorphisms of FAS and FASL may be associated with the presence and severity of LDD.

The effects of age, sex, ethnicity, and spinal level on the rate of intervertebral disc degeneration: a review of 1712 intervertebral discs.

STUDY DESIGN: A gross anatomic and magnetic resonance imaging study of intervertebral disc (IVD) degeneration in fresh cadaveric lumbar spines. OBJECTIVE: The purpose of this study was to find the rate of IVD degeneration. SUMMARY OF BACKGROUND DATA: Age, sex, race, and lumbar level are among some of the factors that play a role in IVD degeneration. The rate at which IVDs degenerate is unknown. METHODS: Complete lumbar spine segments (T11/T12 to S1) were received within 24 hours of death. The nucleus pulposus, anulus fibrosus, cartilaginous and bony endplate, and the peripheral vertebral body were assessed with magnetic resonance imaging and IVD degeneration was graded by two observers from grade 1 (nondegenerated) to grade 5 (severely degenerated) on the basis of a scale developed by Tanaka et al. The specimens were then sectioned and gross anatomic evaluation was performed according to Thompson et al. RESULTS.: A total of 433 donors and 1712 IVDs were analyzed. There were 366 whites, 47 Africans, 16 Hispanics, 4 Asian. There were 306 male and 127 female donors. The age range was 14 to 81 years, (average: 60.5 ± 11.3). For donors greater than age 40, the L5/S1 IVD degenerated at a significantly faster rate of 0.043 per year compared to 0.031, 0.034, 0.033, 0.027 for L1/L2, L2/L3, L3/L4, L4/L5, respectively. For donors younger than 40, L5/S1 IVD degenerated at a significantly faster rate of 0.141/y compared to 0.033, 0.021, 0.031, 0.050 for L1/L2, L2/L3, L3/L4, L4/L5, respectively. Multiple regression analysis revealed that sex had no significant effect on IVD degeneration whereas African ethnicity was associated with lower Thompson score at L1/L2, L2/L3, L3/L4, L4/L5 when compared with whites. CONCLUSION: The relatively early degeneration at L5-S1 in all races and lower Thompson grade in donors of African ethnicity needs further investigation. Factors such as sagittal alignment, facet joint arthritis, and genetics potentially play a role in IVD degeneration.

Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women.

Spinal osteoarthritis including disc degeneration is a very common condition in the axial skeletons of aged people. Recently, spinal osteoarthritis has been shown to be influenced by specific genetic risk factors. Vertebral osteophytes, endplate sclerosis, and intervertebral disc narrowing are recognized as radiographic features of spinal disc degeneration. HAPLN1 is a key component of the cartilage extracellular matrix; thus, variations in this gene may affect the pathogenesis of cartilage-related diseases such as spinal degeneration. Here, we examine the association between an HAPLN1 gene polymorphism and the radiographic features of spinal degeneration. We evaluated the degree of endplate sclerosis, osteophyte formation, and disc space narrowing in 622 Japanese postmenopausal women. Four SNPs in the HAPLN1 gene-in the 5' flanking region, intron 1, intron 2, and intron 4-were analyzed using the TaqMan polymerase chain reaction method. We found that compared to subjects with the CC or CT genotype, those with the TT genotype for an SNP at intron 2 (rs179851) were significantly overrepresented among the subjects with higher scores for osteophyte formation (P = 0.0001; odds ratio 2.12; 95% confidence interval 1.45-3.11, as determined by logistic regression analysis) and disc space narrowing (P = 0.0057; odds ratio 1.83; 95% confidence interval 1.19-2.83). Consistent with the involvement of the HAPLN1 gene in cartilage metabolism, a variation in a specific HAPLN1 gene locus may be associated with spinal degeneration.

The association of aggrecan gene polymorphism with the risk of intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration is now considered to be genetically determined in large part, with environmental factors also playing an important role. The human is known to uniquely exhibit variable numbers of tandem repeat polymorphism within the aggrecan CS1 domain. To date, the analysis of aggrecan's variable numbers of tandem repeat polymorphism has given inconsistent results with respect to the correlation between the allele's size and intervertebral disc degeneration. We wanted to investigate the patterns of the variable numbers of tandem repeat polymorphism in the aggrecan CS1 domain of Koreans, and we analyzed the association between the polymorphism and intervertebral disc degeneration. METHOD: A total of 66 males and 38 females participated in this study. Their ages ranged from 13 to 73 years. Genomic deoxyribonucleic acid was extracted from blood samples and PCR was carried out to detect the alleles of the aggrecan gene. The subjects were evaluated on MRI and they were classified by the number, severity, and morphology of disc degeneration. FINDINGS: The genotyping identified 11 alleles ranging from 21 to 36 repeats. Alleles 13, 18, 19, and 20 were not found in this study. Of the 104 subjects, 29 (28%) were homozygotes and 75 (72%) were heterozygotes. Allele 27 (39%) was the most common form together with alleles 26 (26%) and 28 (14%). The allele 36 is the longest among the alleles ever discovered. For the case that the analysis was limited to subjects with the fourth decades or less, the 21 allele was significantly overrepresented among the persons with multilevel disc degeneration (p < 0.006). CONCLUSIONS: Carrying a copy of the allele with 21 repeats might increase the risk of multiple disc degeneration in the subjects below the age of 40 years.