الفهرس 
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Abstract
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 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 (47) 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 (36) 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-Thourogh systemic and muscloskeletal 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 Lequesne’s algofunctional Index for knee OA (Lequesne., et al 1987).
4-Laboratory investigation:
• Complete blood picture (CBC):
• Erythrocyte sedimentation rate (ESR) :
• Rheumatoid factor (RF):
5-Radiological investigation:
1. Both hands: postroanterior view.
2. Both knees: antroposterior and lateral views.
Grading is done according to the criteria of Kellgren and Lawrence (1957).
6- Genotyping:
• 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).
• There was no statistically significant difference between patients and controls for C\C (p>0.05), while C\T (16) showed a statistically significant difference between the two groups (p<0.01). Thirty patients (63.8%) had T\T genotype versus 36 (100%) of the controls with a statistically significant difference between the two groups (p<0.001).
• In C\T genotype patients:
- There was a significant positive correlation between the Lequesne’s functional score and KL knee radiological grading (r = -0.5, p < 0.05) in patients who had knee OA.
- There was a highly significant positive correlation between AUSCAN functional grading and KL PIP and DIP radiological grading(r = 0.95, 0.98 respectively, p < 0.001) in patients who had hand OA.
- There was no significant correlation between the Lequesene’s knee functional grading and hand AUSCAN functional grading (p > 0.05).
- There was no significant correlation between KL radiological grading of the knee and KL of PIP and DIP joints of the hand (r = 0.19, - 0.45 respectively, p > 0.05).
• In T\T genotype patients:
- 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 knee 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) in patients who had hand OA.
- There was 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 <0.05).
• In Comparisons between genotypes of ILRN gene (SNP rs491589) as regards the clinical and radiological data of OA patients:
- There was a highly statistically significant difference between genotypes as regards age at disease onset where T\T genotype favors onset at an older age (p<0.001).
- In patients with knee OA, there were high statistically significant differences between the genotypes as regards the functional grading (p<0.001) where C\T genotype had higher disability scores than T\T genotype, also there was a high statistically significant difference grading the radiological grading (p<0.001) as C\T genotype had worse grades.
- In patients with hand OA, there was no statistically significant difference between the C\T and T\T genotypes neither in the functional scores (p>0.05), nor in the radiological grading (p>0.05).
• All patients with C\T genotype had an extremely severe grade (100%), while in T\T genotype 15.8% had extremely severe grades with a highly statistically significant difference between both genotypes.