Osteoporosis in beta-thalassemia major patients: role of COLIA1 gene G-T polymorphism

Growth impairment and osteoporosis are serious causes of morbidity in patients with beta-thalassemia major [beta-TM]. Desferoxamine [DFO] toxicity and iron overload have been proposed as the main underlying reasons. G-T polymorphism in regulatory region of COLIA1 gene has recently been associated with reduced bone mass and osteoporotic fractures in postmenopausal women. To detect the possible implication of COLIA1 gene polymorphism in pathogenesis of osteoporosis in beta-TM. Twenty five patients with beta-TM and 20 healthy controls were investigated for the G-T polymorphism of COLIA1 gene using restriction enzyme analysis. Bone mineral density [BMD], growth parameters, serum ferritin level and duration of chelation therapy were also assessed. We detected a heterozygous polymorphism of COLIA1 gene in 12% of beta-TM patients and 25% of the control group. Thalassemic patients had significant lower BMD than normal controls [p < 0.01]. Significant correlation was observed between low BMD and both duration of DFO intake and high ferritin level. Within the control group: Subjects with G/T genotype had significantly lower femoral and lumber BMD than those with G/G genotype. In thalassemic patients: No significant difference was found in BMD between the two COLIA 1 genotypes. We cannot detect evident role for COLIA1 gene polymorphism in the pathogenesis of osteoporosis in this group of beta-TM patients although this role has been detected in the control group. Further studies that include higher number of patients and more than one genetic polymorphism are needed in order to evaluate the role of genetic factors in the pathogenesis of osteoporosis in thalassemic patients

Serum matrix metalloproteinase-3 as a disease activity marker in patients with rheumatoid arthritis

To analyze the clinical significance of measurement of serum matrix metalloproteinase-3 [MMP-3] levels in relation to systemic markers of inflammation, functional status, disease activity parameters and degree of joint damage assessed radiologically in patients with rheumatoid arthritis [RA]. Forty adult patients with RA and 10 healthy controls had serum samples tested with indirect sandwich enzyme-linked immunosorbent assay for MMP-3. Patients were assessed clinically for Ritchie articular index score [RAI], Steinbrocker score, Health Assessment Questionnaire [HAQ], Disease activity score including a 28-joint count [DAS 28] and Chronic arthritis systemic index [CASI]. Then, plain radiograph of both hands and feet were obtained and the mdified Larsen score was used to assess joint damage. Recent C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR] were recorded. MMP-3 level in RA patients was significantly higher than that in the control group [p=0.043]. Serum levels of MMP-3 show significant correlation with disease duration, CRP, ESR, Steinbrocker score, DAS 28 and modified Larsen score [in the two subgroups of patients: erosive and non-erosive]. No correlation was found between MMP-3 levels and patients' age, RAI, HAQ or CASI. MMP-3 is a single variable that correlates with disease activity and seems to be useful for early diagnosis and follow-up of patients with RA