Mannose-binding protein gene polymorphism in South African systemic lupus erythematosus

Davies, E.

doi:10.1093/rheumatology/37.4.465

Cited by 22 publications

(15 citation statements)

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“…Studies included in meta-analysis. Seventeen relevant publications concerning MBL polymorphisms and SLE were identified (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(39)(40)(41)(42). Three studies were excluded because of duplicated data (39) or inadequate description of the genotype data (40,42).…”

Section: Resultsmentioning

confidence: 99%

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The mannose‐binding lectin gene polymorphisms and systemic lupus erythematosus: Two case–control studies and a meta‐analysis

Lee

Witte

Momot

et al. 2005

Arthritis & Rheumatism

154

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Objective. Mannose-binding lectin (MBL) enhances opsonization and activates complement. Dysfunctional alleles of MBL have been associated with low plasma concentrations of MBL and increased risk of systemic lupus erythematosus (SLE), but genotyping studies have shown inconsistent results. We performed case-control studies of the MBL polymorphisms in 2 Caucasian cohorts and a meta-analysis incorporating all published results of MBL genotyping in SLE to explore whether the MBL functional variants are associated with SLE.Methods. MBL genotypes at 7 single-nucleotide polymorphisms were sequenced in 96 European American patients with SLE and 96 age-, race-, and sexmatched controls. MBL codons 52, 54, and 57 were genotyped in 285 German patients with SLE and 200 race-matched controls. Allele frequencies of all known variants were tallied for meta-analysis.Results. Although there was a trend toward association with MBL polymorphisms in both patient cohorts evaluated, none of them was significantly associated with SLE on its own. Seventeen comparisons from 15 studies were included in the meta-analysis. Publication bias was excluded by Egger's regression test (P ‫؍‬ 0.14). The overall odds ratio for MBL codon 54 variant B was 1.406 (95% confidence interval 1.221-1.608; P < 0.001). Stratification by ethnicity showed significantly increased odds ratios for association of the MBL codon 54B variant with SLE in African, Asian, and Caucasian cohorts.Conclusion. Meta-analysis of all available studies on MBL polymorphisms and SLE shows that MBL variant alleles such as MBL exon 1 codon 54 B, promoter -550 L, and promoter -221 X are SLE risk factors. This association is robust and persists after incorporation of data from our 2 cohorts in which the association failed to reach significance.Systemic lupus erythematosus (SLE) is the prototype of human autoimmune diseases. It is a disorder of generalized autoimmunity with unknown etiology, characterized by autoantibody production and immune complex (IC) formation that lead to intense inflammation and multiple organ damage. Although the pathogenesis of SLE remains largely unknown, the significant familial aggregation, high concordance rate among monozygotic twins, and increased relative risk in first-degree relatives of an SLE proband demonstrate the underlying genetic basis of the disease (1,2).Mannose-binding lectin (MBL) is a serum protein of the collectin family that plays an important role in

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Section: Resultsmentioning

confidence: 99%

“…Findings of candidate gene studies of MBL have proved controversial because of inconsistent genetic associations (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). There are several possible explanations for this variability.…”

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confidence: 99%

The mannose‐binding lectin gene polymorphisms and systemic lupus erythematosus: Two case–control studies and a meta‐analysis

Lee

Witte

Momot

et al. 2005

Arthritis & Rheumatism

154

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“…There are several possible explanations for the apparent conflict with our results showing a protective effect of low plasma MBL levels on future risk of VTE. First, MBL deficiency is a predisposing factor for the incidence and severity of systemic lupus erythematosus, as well as the frequency of infectious complications. Systemic lupus erythematosus and acute infectious diseases are associated with increased risk of VTE and may therefore counterbalance the beneficial effect of low MBL levels.…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of mannose‐binding lectin and future risk of venous thromboembolism

Liang

Høiland

Ueland

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Animal and observational studies have suggested a pathophysiological role for complement in venous thromboembolism (VTE), but the initiating mechanisms are unknown. Mannose‐binding lectin (MBL) bound to altered host cells leads to activation of the lectin complement pathway, and both high and low MBL levels have been implicated in the pathophysiology of cardiovascular disease. Objectives To investigate the association between plasma MBL levels and future risk of incident VTE. Methods We conducted a nested case‐control study in 417 VTE patients and 849 age‐matched and sex‐matched controls derived from the general population (Tromsø Study). Plasma MBL levels were measured using enzyme‐linked immunosorbent assay. Logistic regression models were used to estimate odds ratio (OR) for VTE across quartiles of plasma MBL levels. Results Subjects with plasma MBL levels in the lowest quartile (<435 ng/mL) had a reduced OR for overall VTE (OR 0.79, 95% confidence interval [CI]: 0.56‐1.10) and for DVT (OR 0.70, 95% CI: 0.47‐1.04) compared to those with MBL in the highest quartile (≥2423 ng/mL) after multivariable adjustments. For VTE, DVT, and pulmonary embolism (PE) the ORs decreased substantially with decreasing time between blood sampling and VTE event. Conclusions Our findings suggest that low plasma MBL levels are associated with reduced risk of VTE, and DVT in particular.

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“…1 The signal transduction pathway via the T-cell receptor (TCR) has been shown to be altered in MRL lpr/lpr mice. [3][4][5][6][7][8] Defects in signal transduction through the TCR-CD3 complex may cause T-cell dysfunction and autoimmunity in NOD mice as well as in MRL lpr/lpr mice. [3][4][5][6][7][8] Defects in signal transduction through the TCR-CD3 complex may cause T-cell dysfunction and autoimmunity in NOD mice as well as in MRL lpr/lpr mice.…”

Section: Introductionmentioning

confidence: 99%

T-cell receptor ζ mRNA with an alternatively spliced 3′ untranslated region is generated predominantly in the peripheral blood T cells of systemic lupus erythematosus patients

Tsuzaka¹,

Onoda²,

Yoshimoto³

et al. 2002

Modern Rheumatology

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To investigate the mechanism of the downregulation of T-cell receptor chain (TCR ) expression in the peripheral blood T cells (PBTs) of systemic lupus erythematosus (SLE) patients, we analyzed the 3Ј untranslated region (3ЈUTR) of TCR mRNA, because the 3ЈUTR in mRNA is responsible for posttranscriptional regulation. Use of the reverse transcriptase polymerase chain reaction (RT-PCR) to amplify the 917 bp TCR 3ЈUTR cDNA demonstrated that the short variant cDNA (355 bp), expressed as an alternatively spliced 3ЈUTR with 562-bp deletion, was predominated in the PBTs of 11 of 14 SLE patients, whereas mainly the wild-form cDNA (917 bp) was detected in the PBTs of seven negative controls (two systemic sclerosis patients, five normal controls) and in two T-cell line hybridomas. Semiquantitative PCR also revealed the predominant expression of the TCR mRNA with alternatively spliced 3ЈUTR (TCR mRNA/as-3ЈUTR), and a decreased expression of TCR mRNA with the wild form 3ЈUTR (TCR mRNA/w-3ЈUTR) in SLE T cells. However, there was no difference in the expression of the open reading frame (ORF) TCR mRNA between the negative controls and SLE patients. The TCR protein expression level according to Western blot analysis correlated well with that of TCR mRNA/w-3ЈUTR (r ϭ 0.931) and reversibly with TCR mRNA/as-3ЈUTR (r ϭ Ϫ0.614), but not with ORF TCR mRNA (r ϭ Ϫ0.296). It can be concluded that the reduced expression of TCR mRNA/w-3ЈUTR and the predominant expression of TCR mRNA/as-3ЈUTR lead to downregulation of the TCR protein in SLE T cells.

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Mannose-binding protein gene polymorphism in South African systemic lupus erythematosus

Cited by 22 publications

References 0 publications

The mannose‐binding lectin gene polymorphisms and systemic lupus erythematosus: Two case–control studies and a meta‐analysis

The mannose‐binding lectin gene polymorphisms and systemic lupus erythematosus: Two case–control studies and a meta‐analysis

Plasma levels of mannose‐binding lectin and future risk of venous thromboembolism

T-cell receptor ζ mRNA with an alternatively spliced 3′ untranslated region is generated predominantly in the peripheral blood T cells of systemic lupus erythematosus patients

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