Understanding the genetic contribution to OA has two important clinical implications. First, by finding genes involved in disease risk or involved in progression, we will better understand the molecular pathogenesis of OA, which may open areas for therapeutic intervention. Second, by identifying sets of genetic variants associated with risk for disease or with progression of OA, it will be possible to detect individuals at high risk and to monitor disease progression better (Valdes et al., 2008).
The aim of this study was to study the IL1RN gene in patients with hand and/or knee OA to clarify the influence of genetic variations of this gene on risk and severity of osteoarthritic disease. We particularly studied the CC/CT genotype at rs419598 that was reported by Kerkhof et al. (2011) in their meta-analysis to be significantly associated with OA radiographic severity.
Forty seven unrelated Egyptian patients with primary OA (hand and/or knee), were enrolled in this study. They were attending the Rheumatology, Rehabilitation and Physical medicine outpatients’ clinic and inpatients’ department of Benha University Hospitals.
Thirty six apparently healthy subjects recruited from the hospital personnel and relatives of other patients were included in the study as a control group.
• All patients were subjected to:
1- Full history taking:
2-Thorough systemic and musculoskeletal examination
3-Indices of Clinical Severity:
We assessed the clinical severity of hand OA according to the Australian/Canadian (AUSCAN) Hand Osteoarthritis Index (Bellamy et al., 2002), and of knee OA according to the Lequesne’s algofunctional Index for knee OA (Lequesne et al., 1987).
• Complete blood picture (CBC)
• Erythrocyte sedimentation rate (ESR)
• Rheumatoid factor (RF)
1. Both hands: a postroanterior view.
2. Both knees: antroposterior and lateral views.
Grading was done according to the criteria of Kellgren and Lawrence (1957).
6- Genotyping according to SNP rs419598 of IL1RN gene :
• Sample Collection.
• DNA Extraction.
• Estimation of DNA Concentration of the samples.
• Single Nucleotide Polymorphism (SNP) detection.
The results of this study were as follows:
• The patients were 42 females (89.4%) and 5 males (10.6%), whose ages ranged between 48-71 years (mean 59.66 ± 5.9 years). Thirty-nine patients (83%) had knee OA only, while eight patients (7%) had knee and hand OA.
• The controls were 32 females (88.9 %) and 4 males (11.1%), whose ages ranged between 42-66 years (57.81± 6.4 years).
• There were no statistically significant differences between OA cases and controls as regards sex, age and BMI (p > 0.05).
• As regards the genotyping, one patient had CC genotype, 16 patients had CT genotype and 30 patients had TT genotype, while all controls had TT genotype.
• There was no statistically significant difference between patients and controls for CC (p>0.05), while CT (16) showed a statistically significant difference between the two groups (p 0.05).
• In TT genotype patients:
- In patients who had knee OA, there was a highly significant positive correlation between Lequesne’s functional grading score and KL knee radiological grading (r = 0.67 , p < 0.05).
- In patients who had hand OA, there was a highly significant positive correlation between the AUSCAN functional grading and KL PIP, DIP joints radiological grading (r =0.88, 0.98 respectively, p < 0.001).
- There was a highly significant correlation between the knee Lequesene’s functional score and hand AUSCAN functional score (r = 0.62, p > 0.05).
- There was a significant correlation between radiological grading of the knee OA (KL knee) and KL PIP, DIP joints of the hand OA ( r =0.45, 0.46 respectively, p