Candidate gene investigation of spinal degenerative osteoarthritis in Greek population

Few data exist concerning the natural history of degenerative osteoarthritis (OA) of the spine and its associated gene investigation. Degenerative spinal OA demonstrates an international prevalence of 15% in the general population.

The aim of this Greek case-control study is to examine gene polymorphisms that have been previously shown or hypothesized to be correlated to degenerative OA. Gene polymorphisms, especially for OA, have never been previously studied in the Greek population.

The study was conducted from May 2009 to December 2012. Eligible subjects who agreed to take part in the study were Greek adults from all of Greece, referred for consultation to the Palliative Care and Pain Relief Unit of Aretaieion University Hospital, in Athens, Greece.

A total of 601 matched pairs (cases and controls) participated in the study, 258 patients (188 women and 70 men) with clinically and radiologically confirmed degenerative OA and 243 control subjects (138 women and 105 men).

All patients presented with chronic pain at the spine (cervical, thoracic or lumbar) caused by sympomatic osteophytes or disc narrowing, whereas clinical diagnosis of OA was based on the presence of both joint symptoms and evidence of structural changes seen on plain conventional X-rays.

We investigated genetic variation across candidate OA gene GDF5, CDMP1, CDMP2, Asporin, SMAD3, and chromosomal region 7q22, in a sample of 258 patients with clinically and radiologically confirmed degenerative OA, and 243 control subjects from the Greek population. All subjects (patients and controls) were subsequently matched for the epidemiologic, demographic, and clinical risk factors, to prevent selection biases. A tagging single nucleotide polymorphism (SNP) approach was pursued to cover variation across all targeted loci. Single marker tests as well as haplotypic tests of association were performed. There is no conflict of interest, and also, there are no study funding sources.

We found significant association of spine OA with SNPs and haplotypes along the 7q22 chromosomal region and the SMAD3 gene. At 7q22, single marker association tests showed SNPs rs3801954 and rs2023685 to be associated with the disorder (p-value .0312 and .0041, respectively), but only SNP rs2023685 retained a significant p-value (.046) after performing 1,000 permutation tests. At the SMAD3 gene, SNP rs422342 was also found to be statistically associated (p-value .0282) to intervertebral disc degeneration (permutation p-value .042).

This is the first study to investigate genetic variation in relation to spine OA in the Greek population. Our results indicate that the genetic basis of the disease may differ in the Greek population in relation to populations of Asian origin, although larger sample sizes are required to underpin the full extent of the involvement of analyzed loci.