Background. Thrombocytopenic Trombotic purpura (TTP) is a rare disease. In TTP high concentration of multimeric factors cause platelet aggregations. The von willebrant factor (vwf) is a protein synthesized by endothelium and megakaryocytic is present in multimeric forms. Metalloproteinase are involved in cartilage proteolysis and participate in other processes of matrix cellular disruption. Objective. To evaluate polymorphism state in MMP1 (Matrix metalloproteinase-1) promoter gene in heterozygous or homozygous conditions and clinical correspondenceto TTP. Materials and methods. Forty-two consecutive cases with primary Thrombocytopenic trombotic purpura, median 42 year, range 43-82), 29 female, and 13 male were evaluated. DNA was collected from peripheral blood in mono nucleated cells. Saline method with small modification for DNA dried slides extraction was used. PCR method for transcript of a disintegrin and metalloprotease with thrombospondin type I domains 13(ADAMTS13) and beta actin controls were used. For study of MMP1 gene, polymorphism PCR method, and enzymatic ALU I digestions and agarose gel electrophoresis evaluation were used. Results were compared (case control analysis) to 150 (ratio 1:3.5) Sardinian control, matched for age, geographic zone and sex. Results. All transcripts for ADAMTS 13 were positive. The genotype analysis in patients groups (n=42) reveal 3/42 (7,1%) 2G/2G genotype, 25/42 (59.5%) 1G/2G , 14/42 (33,3%) 1G/1G. While in controls (n=150) were 50/150 (33.3%)2G/2G genotype, 66/150 (44.4%)1G/2G genotype, 33/150 (22.2%)1G/1G genotype respectively. Then, from 42/42 cases evaluation was evinced significative (X=7.5808, p=0.005). Respect control groups. On the basis of this observation the 2G/2G patient groups, we suppose a co-operative action between protheolitic activity of collagenase of MMP1 and reduced activity of ADAMTS 13. This could be originated from an increase of transcription activity of MMP1 with an increase of collagenase quantity. This 2G/2G genotype, could be s protective towards TTP disease. In addition and a prompt response to plasmapheresis did not present any relapse in 11,11, 8 years of continuous of follow-up respectively.
Trombocytopenic trombotica purpura (ttp) and metalloproteinase (mmp1). role for a possible proctetive effect
ENNAS, MARIA GRAZIA;
2005-01-01
Abstract
Background. Thrombocytopenic Trombotic purpura (TTP) is a rare disease. In TTP high concentration of multimeric factors cause platelet aggregations. The von willebrant factor (vwf) is a protein synthesized by endothelium and megakaryocytic is present in multimeric forms. Metalloproteinase are involved in cartilage proteolysis and participate in other processes of matrix cellular disruption. Objective. To evaluate polymorphism state in MMP1 (Matrix metalloproteinase-1) promoter gene in heterozygous or homozygous conditions and clinical correspondenceto TTP. Materials and methods. Forty-two consecutive cases with primary Thrombocytopenic trombotic purpura, median 42 year, range 43-82), 29 female, and 13 male were evaluated. DNA was collected from peripheral blood in mono nucleated cells. Saline method with small modification for DNA dried slides extraction was used. PCR method for transcript of a disintegrin and metalloprotease with thrombospondin type I domains 13(ADAMTS13) and beta actin controls were used. For study of MMP1 gene, polymorphism PCR method, and enzymatic ALU I digestions and agarose gel electrophoresis evaluation were used. Results were compared (case control analysis) to 150 (ratio 1:3.5) Sardinian control, matched for age, geographic zone and sex. Results. All transcripts for ADAMTS 13 were positive. The genotype analysis in patients groups (n=42) reveal 3/42 (7,1%) 2G/2G genotype, 25/42 (59.5%) 1G/2G , 14/42 (33,3%) 1G/1G. While in controls (n=150) were 50/150 (33.3%)2G/2G genotype, 66/150 (44.4%)1G/2G genotype, 33/150 (22.2%)1G/1G genotype respectively. Then, from 42/42 cases evaluation was evinced significative (X=7.5808, p=0.005). Respect control groups. On the basis of this observation the 2G/2G patient groups, we suppose a co-operative action between protheolitic activity of collagenase of MMP1 and reduced activity of ADAMTS 13. This could be originated from an increase of transcription activity of MMP1 with an increase of collagenase quantity. This 2G/2G genotype, could be s protective towards TTP disease. In addition and a prompt response to plasmapheresis did not present any relapse in 11,11, 8 years of continuous of follow-up respectively.
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