How Reliable Are the Reported Genetic Associations in Disc Degeneration?: The Influence of Phenotypes, Age, Population Size, and Inclusion Sequence in 809 Patients
| Autor: | S. Rajasekaran, Anita Yee, Ajoy Prasad Shetty, Patrick Y. P. Kao, Rishi Mugesh Kanna, Kenneth M.C. Cheung, Ranjani Raja Reddy, Muthuraja Raveendran, Daniel W. Chan, Senthil Natesan |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Candidate gene medicine.medical_specialty Cross-sectional study Population Intervertebral Disc Degeneration Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Internal medicine Medicine Humans Orthopedics and Sports Medicine Genetic Predisposition to Disease Pyrophosphatases education Intervertebral Disc Genetic Association Studies Genetic association Genetics 030222 orthopedics education.field_of_study Extracellular Matrix Proteins business.industry Age Factors Modic changes Middle Aged Magnetic Resonance Imaging Cross-Sectional Studies Matrix Metalloproteinase 20 Phenotype Sample size determination Cohort Population study Receptors Calcitriol Female Neurology (clinical) ADAMTS5 Protein business 030217 neurology & neurosurgery |
| Zdroj: | Spine. 41(21) |
| ISSN: | 1528-1159 |
| Popis: | Study design Prospective genetic association study. Objective The aim of this study was to document the variations in the genetic associations, when different magnetic resonance imaging (MRI) phenotypes, age stratification, cohort size, and sequence of cohort inclusion are varied in the same study population. Summary of background data Genetic associations with disc degeneration have shown high inconsistency, generally attributed to hereditary factors and ethnic variations. However, the effect of different phenotypes, size of the study population, age of the cohort, etc have not been documented clearly. Methods Seventy-one single-nucleotide polymorphisms (SNPs) of 41 candidate genes were correlated to six MRI markers of disc degeneration (annular tears, Pfirmann grading, Schmorl nodes, Modic changes, Total Endplate Damage score, and disc bulge) in 809 patients with back pain and/or sciatica. In the same study group, the correlations were then retested for different age groups, different sample, size and sequence of subject inclusion (first 404 and the second 405) and the differences documented. Results The mean age of population (M: 455, F: 354) was 36.7 ± 10.8 years. Different genetic associations were found with different phenotypes: disc bulge with three SNPs of CILP; annular tears with rs2249350 of ADAMTS5 and rs11247361 IGF1R; modic changes with VDR and MMP20; Pfirmann grading with three SNPs of MMP20 and Schmorl node with SNPs of CALM1 and FN1 and none with Total End Plate Score.Subgroup analysis based on three age groups and dividing the total population into two groups also completely changed the associations for all the six radiographic parameters. Conclusion In the same study population, SNP associations completely change with different phenotypes. Variations in age, inclusion sequence, and sample size resulted in change of genetic associations. Our study questions the validity of previous studies and necessitates the need for standardizing the description of disc degeneration, phenotype selection, study sample size, age, and other variables in future studies. Level of evidence 4. |
| Databáze: | OpenAIRE |
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