Dissertation committee:
Μυστακίδου Κυριακή, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Κουλουλίας Βασίλειος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πάσχου Περιστέρα, Αναπληρώτρια Καθηγήτρια, Τμήμα Μοριακής Βιολογίας και Γενετικής, Δημοκρίτειο Πανεπιστήμιο Θράκης
Χατζηιωάννου Αχιλλέας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μπατιστάκη Χρυσάνθη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Μαυραγάνη Κλειώ, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ζυγογιάννη Άννα, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Intravertebral disc degeneration (IDD) of the spine demonstrates an interna-tional prevalence of 15% in the general population and over 50% in people aged over 60 years. Modern epidemiological studies have shown that degenerative osteoarthritis is a dis-ease of major concern with a huge economic and social impact, due a variety of reasons and has become the most common cause of prescription of nonsteroidal anti-inflammatory drugs, with all the consequences this entails especially for senior citizens. Gene polymorphisms, es-pecially for clinical and image-confirmed spinal disc degeneration, osteoarthritis of the spine, have never been previously studied in the Greek population.
Aim: The aim of the study was to investigate the risk factors and the genetic background of degenerative osteoarthritis of the spine in the Greek population by detection of specific genet-ic polymorphisms, which may be involved in the etiology of the disease.
Methods: Detailed examination and analysis of GDF5, CDMP1, CDMP2, Asporin, SMAD3 and locus 7q22 genes, of 258 patients (188 female and 70 male) with clinically and radiologi-cally confirmed degenerative osteoarthritis, and 243 control subjects (138 female and 105 male) were done in order to determine the percentage correlation of genetic background deemed responsible in Greece.
Results: Totally, 298 (59.5%) subjects expressed GDF5, 297 (59.4%) the protein SMAD3, 364 (73.1%) the protein ASPN and 468 (93.6%) the chromosome 7q22. Patients suffering from osteoarthritis had significantly higher body mass index (27,9 ± 4,8 versus 26,7 ± 4,8, p <0,05), significantly higher exposure to professionals risks (15.5% vs. 1.2%, p <0,05), signif-icantly more severe physical stress (20.9% compared to 0,8%, p <0,05), never done physical exercise in a significantly greater percentage (77.9% vs 0%, p < 0.05), and suckled at a signif-icantly higher rate (58.3% vs. 0%, p<0,05) compared with controls. Only patients with osteo-arthritis had pain and reported limitation on activity due to pain. Overall, 231 (89.5%) patients had osteoarthritis of the lumbar spine, 165 (64%) in the cervical spine and 82 (31.8%) in the thoracic spine. Patients with osteoarthritis expressed alleles on chromosome 7q22 and protein Smad3. Specifically, significantly more patients in comparison to controls expressed SNPs rs3815148 (64 vs 1, p <0,05), SNPs rs331377 (136 vs 1, p <0,05), SNPs rs17154040 (114 vs 1, p < 0.05), SNPs rs3801954 (130 vs 1, p <0,05) and SNPs rs2023685 (93 vs 0, p <0,05). Single marker association tests, showed SNPs rs3801954 and rs2023685 to be associated with the disorder (p-value 0.0312 and 0.0041 respectively), but only SNP rs2023685 retained a significant p-value (0.046) after performing 1000 permutation tests. Haplotype association tests indicated that haplotypes ATCATCC (p-value 0.0064) and CTTACCT (p-value 0.0105) seem to be associated to IDD and sustained this signal even after performing 1000 permuta-tion tests (permutation p-value 0.006 and 0.011 respectively). Single markers and haplotypes
association tests on SNP rs422342 found it to be statistically (p-value 0.0282) associated to IDD (permutation p-value 0.042).
Conclusions: The risk factors were found to be responsible for the development of osteoar-thritis in Greek population was obesity, heavy physical stress, failure to exercise and manual labor. Most patients had osteoarthritis mainly in the lumbar and cervical spine. Osteoarthritis of patients was due to the expression of alleles on chromosome 7q22 and protein Smad3. The agent GDF5 and the protein Asporin played no significat role in the expression of osteoarthri-tis. This is the first genotyping of these genes thought to be involved in OA for the Greek populace and the results show the genetic basis of OA in Greece is different at least from the Asiatic countries.
Keywords:
Osteoarthritis, Spinal, Protein ASPN, Chromosome 7q22, Agent GDF5, Protein SMAD3, Allele, Genotype
