الفهرس 
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Abstract
SUMMARY
Osteoarthritis (OA) is a chronic degenerative disease, that has been suggested recently as an organ level failure, involving not only cartilage and bone, but also ligaments, menisci, muscles and neural tissues . Although the etiology of OA is incompletely understood, mechanical trauma and altered genetics are involved in the pathogenesis of OA, the immune system and proinflammatory cytokines also might play a part as helper T cells (CD4+) were detected in OA synovium and it is level was similar to that of rheumatoid arthritis (RA) (Nakamura et al., 1999).
Impaired signals of Leptin hormone has been identified as a player in the pathophysiology of OA as it exert its pro-inflammatory and pro-catabolic activities on cartilage (Azamar et al., 2017).
Leptin has been known as a cytokine-like factor with pleiotropic actions that primarily enhance the production of destructive mediators. On the other hand, leptin seems to exert compensatory anabolic responses on cartilage, that is characteristic for the early development of OA (Vuolteenaho et al., 2014).
The importance of LEPR in regulating leptin signal pathway and expression of LEPR within the human cartilage suggested LEPR SNPS as possible genetic risk factor of OA. (Li et al., 2012).
The present study was conducted on 73 Egyptian patients (58 females and 15 males) suffering from primary KOA and 73 age and sex matched healthy control subjects (61females and 12 males). Patients with primary KOA as defined by The ACR classification criteria for OA of the knee and according to the Kellgren-Lawrence (K/L) grading system (≥ 2 scale).
Healthy controls were unrelated Egyptian individuals subjects living in the same geographical region. We obtained Informed consent from all patients and healthy control subjects participating in the study.
All patients included in this study were subjected to full history taking, clinical examination and VAS, WOMAC scores, Laboratory investigations were done in the form of ESR, CRP, lipid profile PCR/RELP for Evaluation of LEPR gene polymorphism for patients and controls, in addition to routine labs, plain x ray for both knees for patients and controls.
Results showed the following:
The mean BMI in patients group was 33,35 Kg/m2 while the mean of BMI in control group was 29,34 Kg/m2 , there was a statistical significantly difference between both groups regarding BMI (P< 0.001).
Analysis of laboratory data, revealed a statistically significant difference on comparing serum triacylglycerol (TAG) of patient and control groups, (the mean was 190 and 90 mg/dL respectively) (P < 0.001). The level of serum cholesterol was higher in KOA group than control group however the difference was statistically insignificant (the mean was 179 and 154 mg/dL respectively) (P > 0.05).
The results of the frequencies distribution of LEPR Gln223Arg genotype variants in both the study and control groups were (P = 0.144 and 0.34, respectively).
In the current case control study, analysis of genetic influence of LEPR Gln223Arg gene polymorphism on the BMI of the patients of primary KOA revealed that carriers of the (AG) genotype had the highest mean (35.14±5.83), while carriers of the (AA) genotype had the mean of (34.16±6.73) and carriers of the (GG) genotype had the mean of (31.59±5.18).the difference among these groups was statistically significant (p value =0.032)
On analysis of the association between LEPR Gln223Arg gene SNP and radiological severity of primary KOA in the study group, we detected that carriers of the (AA) genotype had the highest K/L score compared to carriers of the heterozygous (AG) genotype and carriers of (GG) genotype. The difference among these groups was statistically significant (P=0.044).
However, analysis of the effect of LEPR Gln223Arg gene SNP on disease severity as represented by WOMAC Score, did not reveal any statistically significant difference among KOA patients carrying different genotypes(P= 0.511).
Analysis of the association between the intensity of pain in OA patients (assessed by VAS score), and the LEPR Gln223Arg SNP revealed no statistically significant difference among KOA patients carrying different genotypes (P= 0.384).
A significant positive correlation was found between VAS and disease duration , WOMAC score, KL score, with a statistically significant difference, P value = 0.000 .
There was a statistically significant correlation detected on correlating WOMAC Score with age (p =0.000*) , Correlation Coefficient was ( 0.34) which revealed positive correlation.
There was a statistically significant correlation detected on correlating WOMAC Score with BMI (p =0.026*) , Correlation Coefficient was ( 0.26 ) which revealed positive correlation.
There was a statistically significant correlation detected on correlating WOMAC Score with disease duration (p =0.000*) , Correlation Coefficient was (0.60) which revealed positive correlation.
There was a statistically significant correlation detected on correlating WOMAC Score with K-L Score (p = 0.0005) , Correlation Coefficient was ( 0.32 ) which revealed positive correlation.