Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Japanese

Abstract

Mannose binding lectin (MBL) deficiency may be associated with increased susceptibility to infection and autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, we performed for the first systematic search for mutations in all the four exons of the MBL gene using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. Of 49 healthy Japanese individuals studied, only the previously reported mutation at the codon 54 (substitution from Gly to Asp; G54D) was identified. The allele frequencies of G54D in 105 healthy Japanese individuals, 95 SLE patients and 59 RA patients, were 0.233, 0.226 and 0.178, respectively, which were not significantly different. In addition, two polymorhisms at positions of −550 and −221 in the promoter region were not associated with SLE and RA. It is unlikely that MBL deficiency plays a major role in the pathogenesis of SLE and RA in Japanese. Genes and Immunity (2000) 1, 464-466.Keywords: mannose binding lectin; mannose binding protein; Complement; autoimmune diseases; systemic lupus erythematosus; rheumatoid arthritis Mannose binding lectin (MBL), also known as mannose or mannan binding protein, is a member of the collectin family of proteins, characterized by the presence of collagen-like domains and carbohydrate recognition lectin domains. 1 MBL binds to high mannose and Nacetyl-glucosamine oligosaccharides present on the cell surface of yeasts, bacteria and viruses and serves as the initiator of the third pathway of complement system (lectin pathway). 2 MBL is considered to be involved in the innante immunity of host defence that works prior to the establishment of adaptive immune system. Previous studies suggest that homozygous deficiency of MBL is associated with recurrent infections in children 3,4 as well as increased susceptibility and shorter survival of human immunodeficiency virus (HIV) patients. 5,6 Although there are controversies, association of MBL deficiency with chronic hepatitis virus type B (HBV) infection 7 and its progression, 8 and with poor response to interferon in chronic hepatitis virus type C (HCV) 9 has also been reported. In addition MBL deficiency has also been implicated in the pathogenesis of autoimmune diseases. Studies in the UK and Spanish

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

“…Only the polymorphism at codon 54 was identified, which is in consistent with the previous findings that no polymorphisms at codons 52 and 57 were identified in Japanese. 20,29 Of the three structural gene polymorphisms at codons 52, 54, and 57, the codon 54 variant has been shown to be predominant in Caucasians (allele frequency 0.11-0.16) and Asians (allele frequency B0.2 in our study), while the codon 57 mutation is mostly identified in Africans in even higher frequencies (0.23-0.29). 4 The codon 52 variant occurs in much lower frequencies in both Caucasians and Africans (allele frequency 0.05 or less).…”

“…c: bacterial pneumonia (two patients), sepsis (one patient), and bacterial meningitis (one patient). 20 The numbers of patients with major infection as well as the kind of infection are shown in Table 1.…”

Association of mannose-binding lectin gene (MBL2) polymorphisms with rheumatoid arthritis in an Indian cohort of case-control samples

“…Stanworth et al (1998) found no association between MBL2 polymorphisms and RA, whereas Kilpatrick (2002) reported higher MBL2 concentrations in the sera of RA patients compared with healthy controls. Horiuchi et al (2000) reported that MBL2 gene polymorphisms were not risk factors for systemic lupus erythematosus (SLE) or RA in Japanese individuals, whereas Tsutsumi et al (2001) found that the frequency of allele B in the patient group was mildly increased in SLE, but with RA, the number of patients homozygous for allele B were slightly increased with no statistical significance. No evidence of an association of MBL2 polymorphisms or serum MBL2 level with RA is available for an Indian population.…”

Biomarkers in systemic lupus erythematosus: I. General overview of biomarkers and their applicability

“…MBL is an acute-phase protein that participates in complement activation and opsonization of antigens. MBL gene polymorphisms have been found to confer increased risk for SLE in all studies (55-64) except for 1 study of Japanese patients (65). A meta-analysis of 8 studies showed that variant alleles conferred a 1.6-fold overall increased risk for SLE (55).…”