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1.
Mannose-binding lectin and rheumatoid arthritis in southern Chinese   总被引:11,自引:0,他引:11  
OBJECTIVE: Insufficiency of mannose-binding lectin (MBL) is associated with recurrent infections. Rheumatoid arthritis (RA) may represent an aberrant immune response to infections. This study examined the phenotypic expression and variant alleles of the MBL gene and its etiologic role in Chinese with RA. METHODS: We studied 211 RA patients and 196 healthy subjects. Serum MBL concentrations and codon-54 mutation of the MBL gene and its promoter polymorphisms were analyzed. Clinical characteristics and disease activity were also examined. RESULTS: Patients with RA had significantly lower serum MBL levels and higher frequency of codon-54 mutation of the MBL gene compared with controls. Additionally, there was a significant difference in the distribution of promoter polymorphisms, H/L, between RA patients and controls, although the frequencies of Y/X and those of nonstructural polymorphisms, P/Q, did not differ between the 2 groups. Furthermore, patients with RA had a lower incidence of the highest-producing haplotype HY and a higher incidence of the lowest-producing haplotype LX compared with controls. Serum MBL levels did not correlate with drug treatment or with disease activity. However, patients with erosive and serious extraarticular disease had significantly lower serum MBL levels than those without these disease manifestations at the time of study. Also, significantly more patients with erosive disease had a codon-54 mutation of the MBL gene compared with those with nonerosive disease. CONCLUSION: The codon-54 mutation and low-producing promoter polymorphisms of the MBL gene are associated with RA. A low serum level of MBL predisposes to the development of RA and is a risk factor for severe disease in southern Chinese.  相似文献   

2.
BACKGROUND/AIMS: The mannose-binding lectin (MBL) gene was reported to play an important role in determining the clinical outcome of persistent hepatitis B virus (HBV) infection. We investigated serum MBL concentrations and MBL gene mutations to determine whether they were related to the prognosis of patients with fulminant hepatic failure (FHF) caused by HBV infection. METHODS: We investigated serum MBL concentrations and MBL gene mutations in 43 HBV-infected Japanese patients with FHF and 260 HBsAg-negative healthy controls. Serum MBL concentrations were measured by an enzyme-linked immunosorbent assay, and mutations in the MBL gene were analysed by nested PCR and direct DNA sequencing. RESULTS: Only a mutation in codon 54 of the MBL gene was found. The frequency of this mutation in nonsurvivors (40%, 8/20) was higher than in survivors (13%, 3/23), and the difference was slightly significant (p = 0.043). The H allele frequency in survivors (70.5%, 31/44) was higher than in nonsurvivors (39.5%, 15/38) (p = 0.0048). Because of these factors the mean serum MBL concentration in survivors, 1.61 ,micro/ml (range 0.3-3.86), was significantly higher than in nonsurvivors, 0.79 microg/ml (range 0.04-1.51) (p < 0.0001). The likelihood ratio for nonsurvival was 0 for over 2.0 microg/ml, 0.67 for 1.0-2.0 microg/ml, and 2.24 for 0-1.0 microg/ml. CONCLUSIONS: The mutation in codon 54 of the MBL gene tended to be higher in nonsurvivors than in survivors. The H allele frequency (high producing allele in H/Y) in survivors was higher than that in nonsurvivors. High levels of serum MBL correlated with the survival of patients with FHF due to HBV infection. Serum MBL may be useful as a predictive factor for the survival of patients with FHF caused by HBV.  相似文献   

3.
OBJECTIVE: Mannose binding lectin (MBL) and FcgammaRII (CD32) polymorphisms have both been implicated as candidate susceptibility genes in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the relationship of these polymorphisms with SLE. METHODS: We studied a cohort of 125 SLE patients from Barcelona, Spain and 138 geographically matched controls. Sequence-specific primer-polymerase chain reaction (SSP-PCR) amplification was used to determine CD32 and MBL structural polymorphisms. MBL haplotypes were established using sequence-specific oligonucleotide probing techniques. RESULTS: Patients carried the MBL codon 54 mutant allele more frequently than controls [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.2-4.0; P=0.007] and the haplotype HY W52 W54 W57 was found to be significantly lower in cases compared with controls (OR 0.6; 95% CI 0.4-0.9; P=0.016). CONCLUSION: The MBL gene codon 54 mutant allele appears to be a risk factor for SLE, whilst haplotypes encoding for high levels of MBL are protective against the disease. Differences between controls and patients were not significant when considering the FcgammaRIIa polymorphisms; similar results were observed for renal affectation.  相似文献   

4.
OBJECTIVE—To investigate polymorphisms of both codon 54 allele and promoter variants of the mannose binding lectin (MBL) gene in patients with primary Sjögren''s syndrome (SS).METHODS—Polymorphisms of codon 54 allele and promoter variants of the MBL gene in 104 patients with SS and 143 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism and allele specific polymerase chain reaction respectively.RESULTS—The allele frequency of the wild type of MBL codon 54 was significantly higher in patients with SS than in controls (0.836 v 0.741; p=0.011), and the frequency of the homozygous wild type of MBL codon 54 was significantly higher in patients with SS than in controls (0.692 v 0.539; p=0.024). On the other hand, the allele frequencies of the MBL promoter gene did not differ between patients and controls (χ2=4.01, df=2, p=0.135).CONCLUSION—The polymorphism of the MBL gene may be one of the genetic factors that determines susceptibility to SS.  相似文献   

5.
Abstract: Background/Aims: The mannose‐binding lectin (MBL) gene was reported to play an important role in determining the clinical outcome of persistent hepatitis B virus (HBV) infection. We investigated serum MBL concentrations and MBL gene mutations to determine whether they were related to the prognosis of patients with fulminant hepatic failure (FHF) caused by HBV infection. Methods: We investigated serum MBL concentrations and MBL gene mutations in 43 HBV‐infected Japanese patients with FHF and 260 HBsAg‐negative healthy controls. Serum MBL concentrations were measured by an enzyme‐linked immunosorbent assay, and mutations in the MBL gene were analysed by nested PCR and direct DNA sequencing. Results: Only a mutation in codon 54 of the MBL gene was found. The frequency of this mutation in nonsurvivors (40%, 8/20) was higher than in survivors (13%, 3/23), and the difference was slightly significant (p = 0.043). The H allele frequency in survivors (70.5%, 31/44) was higher than in nonsurvivors (39.5%, 15/38) (p = 0.0048). Because of these factors the mean serum MBL concentration in survivors, 1.61 μg/ml (range 0.3–3.86), was significantly higher than in nonsurvivors, 0.79 μg/ml (range 0.04–1.51) (p < 0.0001). The likelihood ratio for nonsurvival was 0 for over 2.0 μg/ml, 0.67 for 1.0–2.0 μg/ml, and 2.24 for 0–1.0 μg/ml. Conclusions: The mutation in codon 54 of the MBL gene tended to be higher in nonsurvivors than in survivors. The H allele frequency (high producing allele in H/Y) in survivors was higher than that in nonsurvivors. High levels of serum MBL correlated with the survival of patients with FHF due to HBV infection. Serum MBL may be useful as a predictive factor for the survival of patients with FHF caused by HBV.  相似文献   

6.
OBJECTIVE: To test the hypothesis that low serum mannose-binding lectin (MBL) levels, as a result of the single-nucleotide polymorphisms in the promoter region (-221 X/Y) and exon 1 (codon 54 A/B) of the MBL2 gene, predispose to infection in Chinese patients with systemic lupus erythematosus (SLE). METHODS: Two hundred forty-five patients with SLE were prospectively followed for the development of major infective episodes that required hospitalization and antibiotic treatment during 1992-2005. MBL genotypes were determined by polymerase chain reaction and serum MBL levels were measured by ELISA. RESULTS: In total, 254 major infections developed in 130 patients. Serum MBL levels were shown to correlate inversely with the number of bacterial infections (r = -0.13, p = 0.03). The distribution of MBL genotypes was similar in patients with and without major infection (p = 0.84). Patients with major infection also had more major lupus exacerbations that required daily prednisolone dose > or = 15 mg. Logistic regression showed that log MBL level (odds ratio 0.516, 95% confidence interval 0.305-0.873; p = 0.01) and major lupus exacerbation (OR 1.382, 95% CI 1.154-1.654; p < 0.001) were independent risk factors to major bacterial infection after adjustment for age and disease duration. Multiple regression analysis showed an increase in risk of bacterial infection by 34.2% for every decrease in serum MBL level by one log, and by 22.8% for each increase in number of major lupus exacerbations. CONCLUSION: Low serum MBL level predisposes Chinese patients with SLE to more major infections, in particular bacterial ones.  相似文献   

7.
OBJECTIVE: To investigate whether development of systemic lupus erythematosus (SLE), its clinical manifestations, and autoantibody production are associated with polymorphisms of the mannose-binding lectin (MBL) gene in North American patients with SLE. METHODS: MBL gene polymorphisms in codons 52 (designated variant D, with the wild-type designated A), 54 (variant B), and 57 (variant C) were determined by polymerase chain reaction-sequence specific priming in 130 patients with SLE and 142 healthy controls. Autoantibodies against double-stranded DNA (dsDNA), Smith antigen, phospholipids, Ro/SSA, La/SSB, and RNP were tested at certified clinical pathology laboratories. RESULTS: A statistically significant increased likelihood of anti-Smith antibody production was observed in SLE patients with the heterozygous A/B genotype [odds ratio (OR) 5.1; 95% confidence interval (CI) 1.6-16.6; the A/A genotype as the reference group] or A/C genotype (OR 8.2; 95% CI 2.0-33.9). SLE patients with the homozygous or compound heterozygous variant genotype (O/O; O, a common designation for variant alleles) had an increased likelihood of mounting autoantibody responses against dsDNA, Ro/SSA, and La/SSB, and were more likely to have a history of renal disease (OR 4.8; 95% CI 0.9-25.2). However, differences in the frequencies of MBL variant alleles and genotypes observed between patients with SLE and controls did not reach statistical significance. CONCLUSION: A significantly increased prevalence of anti-Smith antibody was associated with the heterozygous genotypes A/B and A/C. Although MBL structural gene polymorphism was not a risk factor for SLE development in this study population, homozygosity of MBL variant alleles may be a weak disease-modifying factor, particularly for renal involvement, in North American patients with SLE.  相似文献   

8.
Background Mannan-binding lectin (MBL) is believed to be an important constituent of the innate immune system. It has been reported that the codon 54 G/A polymorphism of exon-1 affects the MBL2 gene and alters its activity. Aims We investigated the association between polymorphism of the MBL2 gene and gastric cancer risk as well as Helicobacter pylori infection in a Japanese population. Methods The study cohort comprised 388 gastric cancer patients and 144 healthy volunteers. Polymorphism at codon 54 of exon 1 of the MBL2 gene was investigated by PCR-based restriction fragment length polymorphism analysis. Results There was no significant difference in the distribution of the MBL2 genotype among the gastric cancer patients and healthy controls. However, the carrier of the A allele was more prevalent among patients with a more advanced stage gastric cancer [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.05–2.67; P = 0.03] and also had an increased risk of gastric cancer among patients 65 years of age or younger (OR = 1.6, 95%CI = 1.01–2.52, <0.05). Conclusion The codon 54 polymorphism of the MBL2 gene is associated with more advanced phenotypes of gastric cancer and the risk of gastric cancer in Japanese patients 65 years of age or younger.  相似文献   

9.
OBJECTIVE: To determine whether variant alleles in the coding portion of the mannose-binding lectin (MBL) gene are associated with increased susceptibility to systemic lupus erythematosus (SLE) and concomitant infections. METHODS: MBL alleles and serum concentrations were determined by polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in 91 Danish patients with SLE and in 250 controls. RESULTS: Homozygosity for MBL variant alleles was observed in 7.7% of the SLE patients compared with 2.8% of the controls (P = 0.06), while no difference was seen for heterozygosity (33.0% versus 34.4%). Homozygotes had an increased risk of acquiring serious infections compared with patients who were heterozygous or homozygous for the normal allele (odds ratio 8.6, 95% confidence interval 1.5-47.6, P = 0.01). The time interval from the diagnosis of SLE to the first infectious event was shorter (P = 0.017), and the annual number of infectious events was 4 times higher, among homozygotes (P = 0.00002). They were especially prone to acquire pneumonia (P = 0.00004). CONCLUSION; Homozygosity for MBL variant alleles may explain much of the increased risk of complicating infections seen in SLE patients. Additionally, it is a minor risk factor for acquiring SLE.  相似文献   

10.
Severe infections related to treatment are common in patients with multiple myeloma (MM). Genetic polymorphisms of the immune system may influence the risk of infections. Mannan-binding lectin (MBL) is part of the innate immune system, and individuals homozygous for wild-type MBL encoding gene (MBL2) have a well-functioning MBL pathway of complement activation, in contrast to individuals carrying one or two variant alleles. We evaluated 113 courses of high-dose melphalan and autologous stem cell transplantation (ASCT) in patients with MM. Patients homozygous for wild-type MBL2 had a significantly reduced risk of septicaemia during the ASCT procedure compared with patients carrying variant MBL2: Odds Ratio (OR) 0.19 (95% CI: 0.04-0.77), (P=0.02) in multivariate analysis. The risk of Common Toxicity Criteria grade 3-4 infections in general was not affected by wild-type MBL2: OR 1.20 (95% CI: 0.52-2.78), (P=0.67). The findings indicate that MBL to some extent protects against the most severe infections during ASCT.  相似文献   

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