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Association Of IgA Nephropathy With Matrixmetalloproteinase-9 C-1562T Gene Polymorphism Of Han Nationality In Changchun In China

Posted on:2011-02-15Degree:MasterType:Thesis
Country:ChinaCandidate:X H GengFull Text:PDF
GTID:2144360305954487Subject:Clinical Medicine
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Background: IgAN is a group with the same pathological features of glomerular immune clinical syndrome. It is one of the most common primary glomerular diseases in the world. China is a higher incidence of IgAN. Tracking IgAN more than 20 years, about 20-50% of patients progress to end stage renal failure. So far the mechanism of this disease is not fully clear. Environmental, genetic, individual susceptibility affect the occurrence and development of the disease. Genetic factors play an important role in the process and susceptibility of IgA nephropathy. The molecular genetics research in IgA nephropathy has gradually become concerned areas at home and abroad. MMPs are a group of degradation of extracellular matrix molecules of zinc-dependent neutral protease family. MMP-9 is an important one of MMPs. IV collagen is the most abundant type in the content of glomerular ECM. MMP-9 is one of the most important enzymes degrading Iv collagen, impacting the molecular conformation and functional status of GBM, and closely related to renal damage. MMP-9 genotype may determine the expression of MMP-9, showing functional differences and thus influence the final biological effects of MMP-9 enzyme. Up to now, there are no related report between MMP-9 C-1562T gene polymorphism and kidney disease. Exploring the gene expression or influencing factors of activated expression product may contribute to understanding the pathogenesis of IgA nephropathy.Objective: To explore the correlation between Matrix Metalloproteinase-9 C-1562T (MMP-9 C-1562T)gene polymorphism and IgA nephropathy in Han people living in Changchun of China.Methods: MMP-9C-1562T gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 88 patients with IgA nephropathy and 133 healthy individuals. The genotype and allele frequency in the two groups were compared, and the correlations of IgA nephropathy genotype with clinical manifestations of pre-infection, gross hematuria, renal area pain, hypertension, renal fuction change, confirmed to clinical features of nephritic syndrome or not and the degree of microscopic hematuria, proteinuria, renal function and Lee's pathological grade were analyzed. the correlations between IgAN pathological grade and clinical manifestations were furtherly analyzed. Distribution frequency of genotypes and allele frequencies was figured by gene counting method. Group representation of gene frequency were proved by Hardy-Weinberg equilibrium method. Measurement data are expressed by mean±standard deviation (SD), analyzed by t test and rank sum test.χ2 test was used in comparison of count data. A P value <0.05 was considered statistically significant.Results: The MMP-9 C-1562T genotype frequency distribution in patients of Han nationality in Changchun of China with IgA nephropathy was that CC genotype occurred in 65 patients (73.9 %), CT genotype in 23 patients (26.1%), but TT genotype was not present. The MMP-9 genotype distribution in patients with IgA nephropathy was conducted by Hardy-Weinberg genetic equilibrium testing, genotype frequency distribution not deviated from Hardy-Weinberg equilibrium. The MMP-9 C-1562T genotype frequency distribution in healthy individuals of the same region was that CC genotype occurred in 77 individuals (57.9%), CT genotype in 53 individuals (39.9%), TT genotype in 3 individuals (2.2%). There were significant differences in MMP-9 C-1562T genotype frequency distribution between the two groups (P<0.05). Allele C frequency in the two groups were 86.9% and 77.8%, and allele T frequency were 13.1% and 22.2%, respectively. There were significant differences in allele C and T frequency between the two groups (P<0.05). 88 cases of IgA nephropathy among patients included 47 males and 41 females, male: female=1.15:1, aged 20 to 68 years, mean (34.49±15.06) years. There are no significant differences between two genotypes of IgA nephropathy MMP-9 CC and CT type and gender with age (P> 0.05). CC and CT genotype was associated with proteinuria in IgA nephropathy (P<0.05), unassociated with other clinical manisfestations of pre-infection, gross hematuria, renal area pain, hypertension, renal fuction change, RBC count, confirmed to clinical features of nephritic syndrome and pathological classification. (P> 0.05 ). The five pathologic classification of IgA nephropathy maybe associated with Creatinine and Urea nitrogen (P<0.05), unassociated with other clinical manifestations (P>0.05).Conclusion: 1. Matrixmetalloproteinase-9C-1562T gene polymorphism with health Han nationality in Changchun of China is present, the highest frequency of CC genotype, CT genotype following, the lowest frequency of TT genotype. 2. Matrixmetalloproteinase-9 C-1562T gene polymorphism with IgA nephropathy of Han nationality in Changchun of China also is present, the higher frequency of CC genotype, low frequency of CT genotype, TT genotype was absent. The distribution of the MMP-9 C-1562T gene polymorphism between IgA nephropathy patients and healthy people has statistical significance. C allele may be susceptibility gene of IgA nephropathy. 3. In clinical, there were significant differences between IgA nephropathy MMP-9 C-1562T genotype and 24-hour urinary protein. IgA nephropathy MMP-9 C-1562T genotype can affect the levels of urine protein, unassociated with other clinical manifestations, and not determining the prognosis. Strengthen the non-genetic factors may postpone the occurrence and progress of IgA nephropathy. 4. Pathologically, there was no correlation between IgA nephropathy in patients with MMP-9 C-1562T genotype and pathological grading. 5. Five pathological grading in IgA nephropathy was associated with renal function changes, Providing basis for judging prognosis and clinical treatment.
Keywords/Search Tags:matrix metalloproteinase -9 C1562T gene, genetic polymorphism, Han nationality, IgA nephropathy
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