Genetic variations in plasminogen activator inhibitor-1 gene and beta fibrinogen gene associated with glomerular microthrombosis in lupus nephritis and the gene dosage effect / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship of plasminogen activator inhibitor-1 (PAI-1) gene -675 4G/5G and beta fibrinogen gene -455 G/A variations to glomerular microthrombosis(T) in lupus nephritis(LN).</p><p><b>METHODS</b>One hundred and one patients with biopsy proven LN were divided into two groups according to the presence or absence of glomerular microthrombus, i.e. group LN+T(n=46) and group LN-T(n=55). The genotypes of PAI-1 gene and beta fibrinogen gene were profiled by polymerase chain reaction-sequence length polymorphism (PCR-SLP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. Clinical baseline data at the time of renal biopsy were collected. Normal controls consisted of 128 unrelated healthy adults. The etiologic fractions (EF) were calculated for estimating the contribution of risk genotypes of the two candidate genes to an increase in susceptibility to glomerular microthrombosis in LN patients.</p><p><b>RESULTS</b>Both the 4G/4G genotype and the 4G allele of PAI-1 gene occurred more frequently in group LN+T (47.83% and 0.685) than in group LN-T (23.64% and 0.507)(P<0.05) and normal controls (28.13% and 0.570) (P<0.05). The PAI-1 4G/4G genotype was significantly associated with microthrombosis (OR=2.96, 95%CI:1.26-6.92). Besides, the prevalence of the genotypes carrying the A allele of beta fibrinogen gene, i.e. G/A and A/A, as well as the prevalence of the A allele per se, was increased in group LN+T (47.83% and 0.261) versus group LN-T (27.27% and 0.145)(P<0.05). LN patients carrying the A allele had a high risk of glomerular thrombosis(OR=2.44, 95%CI:0.98-5.59). In addition, the presence of the PAI-1 4G/4G genotype together with the A allele of the beta fibrinogen gene was found to be a greater risk factor (OR=4.5, 95%CI: 1.34-15.12) for glomerular thrombosis in LN than the 4G/4G genotype or the A allele alone. The pooled EF (45.98%) for the risk genotypes of both PAI-1 gene and beta fibrinogen gene was also higher than that for the risk genotypes of either gene (31.67% and 28.23%).</p><p><b>CONCLUSION</b>The above findings indicated that genetic variations in PAI-1 and beta fibrinogen loci might represent risk factors for glomerular microthrombosis in LN. They may have synergetic impact and present gene dosage effect on the susceptibility to this pathological subphenotype.</p>

Genetic variation of mannose-binding protein associated with glomerular immune deposition in IgA nephropathy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the relationship between codon 54 gene polymorphism of the host defense molecule, mannose-binding protein (MBP), and the patterns of glomerular immune deposition in IgA nephropathy (IgAN).</p><p><b>METHODS</b>IgAN patients with different patterns of glomerular immune deposition were selected and divided into two groups. Group A consisted of 77 patients with glomerular IgA and C3 deposits, and Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. Clinical features and laboratory relevant data of all patients were collected. One-hundred and forty healthy adults were recruited as normal controls. The MBP gene codon 54 GGC/GAC polymorphism was investigated by using polymerase chain reaction and restriction fragment length polymorphism.</p><p><b>RESULTS</b>The genotype frequency of GGC/GAC heterozygotes was significantly higher in Group AGM as compared with that of Group A (41.4% vs 19.5%, P < 0.01) or normal subjects (41.4% vs. 26.4%, P < 0.05), while no difference was found in the distribution of MBP genotypes between Group A and normal subjects. GAC allele frequency was also higher in Group AGM than that in Group A (0.24 vs. 0.14, P < 0.05) or normal subjects (0.24 vs. 0.15, P < 0.05). The variant allele (GAC) was markedly associated with Group AGM (OR = 1.95, 95% CI: 1.06 - 3.58). In both Group A and Group AGM, more patients carrying the variant allele had episodes of upper respiratory or gastrointestinal infections prior to the onset of IgAN than those with wild homozygotes (GGC/GGC).</p><p><b>CONCLUSIONS</b>Genetic variation of the host defense molecule, MBP, may be involved in the formation of the diverse patterns of glomerular immune deposition in IgAN. The variant allele of the MBP gene may partially account for abundant immune deposits in some IgAN patients.</p>

Clinical manifestations and pathological characteristics of lipoprotein glomerulopathy / 中华肾脏病杂志

Objective To further elucidate the clinical manifestations and pathological characteristics of lipoprotein glomerulopathy (LPG) . Methods Data of 7 LPG patients were reviewed retrospectively. Clinical manifestations were recorded on the day of renal biopsy. Biochemical profiles of lipid and lipoproteins were examined. Plasma concentration of apoE was determined with radial immunodiffusion assay. Biopsy specimens were processed for light microscopy, immunohistochemistry staining and electron microscopy. Glomerular deposition of apoA, apoB and apoE were detected using monoclonal antibodies on cryostatic sections in all patients. Results All the seven patients presented with edema, microscopic hematuria, heavy proteinuria, anemia and enlarged kidney size. Most of them, the levels of serum creatinine were normal. Biochemical profile revealed that the levels of triglyceride, apoB and apoE were elevated markedly. In all cases, increments of glomerular size and lipoprotein thrombi that occupied capillary lumica in the glomeruli were observed. Immunohistochemistry staining showed that the thrombi were strongly positive for apoA, apoB and apoE. Granules and various size of vacuoles in the thrombi were observed under electronic microscopy. Conclusion Compared with the previous reports of LPG from other countries, some unique clinical and pathological features are found in this group of Chinese LPG patients.