Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL

Matsushita, Masanao; Hijikata, Makoto; Ohta, Yasuhiko; Iwata, Kouichirou; Matsumoto, Masahiro; Nakao, Kuniaki; Kanai, Koichi; Yamada, Nobuhiro; Baba, Kiyoshi; Mishiro, Shunji

doi:10.1007/s007050050320

Cited by 70 publications

(68 citation statements)

References 20 publications

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“…Serum levels of MBL were measured in 249 Japanese individuals whose MBL genotype was determined as previously reported [14,51]. Samples of peripheral blood were taken after obtaining informed consent and were used for MBL genotyping and determination of serum MBL concentration.…”

Section: Samplesmentioning

confidence: 99%

“…These mutations are thought to interfere with the maintenance of a stable quarternary structure and to promote degradation in the circulation [10][11][12] or to impair secretion [11,13], leading to the MBL deficiency. Among Japanese subjects, only one mutation at codon 54 has been reported [14][15][16][17][18]. Polymorphisms in the promoter region or in the untranslated region of the MBL gene also affect the level of MBL [19].…”

Section: Introductionmentioning

confidence: 99%

“…At first, it was thought that Japanese have no MBL mutations [29]. However, it was later shown that mutations exist among the Japanese as well [14][15][16][17][18]. The present study was initiated to elucidate why MBL is detectable in individuals with an MBL mutation using our ELISA system.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

et al. 2003

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Mannose-binding lectin (MBL) activates complement through MBL-associated serine proteases (MASP). A deficiency in MBL due to mutations at exon 1 of the human MBL gene is reported to cause vulnerability to infection. We examined sera of known MBL genotype by gel filtration and assessed their elution patterns using an ELISA for MBL and identified two MBL forms, a high-molecular-mass form and a lower-molecular-mass form. By the identification of either or both forms in individual sera, three types of patterns emerged: type 1 consisted of a high-molecular form; type 2, of a low-molecular form; and type 3, of both forms. Types 1, 2 and 3 corresponded, respectively, to a wild type (A/A), a homozygous mutation at codon 54 (B/B) and their heterozygote (A/B). One exception was a heterozygous LXPA/LYPB phenotype that exhibited the type-2 pattern. Binding to mannan and MASP-1/3 occurred exclusively with the high-molecular form. An apparent MBL deficiency does not in fact represent a deficiency in MBL molecules but rather the presence of circulating oligomeric mutant MBL with impaired function.

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Section: Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

et al. 2003

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“…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.…”

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confidence: 99%

“…The frequency of homozygous and heterozygous G54D mutation in our 105 healthy individuals was 9.5% and 27.6% with the allele frequency of 0.233, which was almost completely identical with those in the previous report in the Japanese 218 healthy individuals. 9 It is likely that the incidence of G54D mutation is more frequent in Japanese than those in the Caucasians and Hong Kong Chinese whose ranges are reported to be 0.11 to 0.16. 16 In Africans, the G54D mutation is not common (less than 0.03) and the mutation at codon 57 (G57E) occurs at comparable frequencies with the range of 0.23 to 0.29.…”

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

et al. 2000

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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

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Haplotype-taggingRANTES gene variants influence response to antiviral therapy in chronic hepatitis C

et al. 2004

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The response to antiviral therapy for chronic hepatitis C virus (HCV) is complex and is determined by both environmental and genetic factors. Recently, interacting gene polymorphisms of the chemokine RANTES have been shown to affect HIV disease progression. Our aim was to assess if these RANTES variants are associated with response to anti-HCV therapy. Three linked RANTES single nucleotide polymorphisms (403 G/A, Int1.1 T/C, and 3 222 T/C) were determined in 297 Caucasian patients who were treated for chronic HCV infection and 152 control subjects. Characteristic nucleotide combinations on single chromosomes (haplotypes) were reconstructed and tested for disease association. Four common RANTES haplotypes (prevalence 73%) were identified in patients and controls. There was a strong association of RANTES haplotype distribution with outcome of antiviral combination therapy (P ‫؍‬ .007). Specifically, RANTES haplotypes carrying Int1.1 C and 3 222 C alleles were more frequent in nonresponders than in patients with a sustained response to antiviral therapy (odds ratio 1.9, P ‫؍‬ .01). The influence of these RANTES haplotypes on the outcome of therapy was more pronounced in patients infected with HCV genotypes 1 and 4 (odds ratio 2.3, P ‫؍‬ .02). Because RANTES haplotypes carrying Int1.1 C are known to down-regulate RANTES transcriptional activity in vitro, the haplotype analysis fits the hypothesis of a diminished T helper 1 lymphocyte response in patients with a negative response to antiviral therapy. In conclusion, RANTES haplotypes might contribute to the polygenic interaction between HCV and the host immune system and could help to risk stratify patients prior to antiviral therapy. ( T he CC chemokine RANTES (regulated on activation normally T cell expressed and secreted; systematic name CCL5) attracts T lymphocytes to inflamed tissues and is produced by T lymphocytes, monocytes, fibroblasts, and endothelial cells. 1,2 In hepatitis C virus (HCV)-infected liver RANTES messenger RNA has been shown to be up-regulated, and its intrahepatic expression levels correlate with serum alanine aminotransferase activities. 3,4 Furthermore, expression of full-length HCV complementary DNA induces the expression of RANTES in hepatocyte cell lines, 5 possibly mediated through activation of nuclear factor B. 6 Interestingly, a 32-base pair deletion in the gene of the CC chemokine receptor 5 (CCR5 ⌬32), which results in decreased receptor expression, 7 has recently been linked to a negative response to interferon monotherapy in hepatitis C. 8 Because the CCR5 ligand RANTES preferentially attracts T helper 1 lymphocytes, 9 RANTES might also be associated with treatment response to antiviral therapy, which is thought to depend on a sufficient proinflammatory cytokine response. 10,11 The human RANTES gene spans 8.5 kb on chromosome 17q11-q12 and has the characteristic three exons/ two introns organization of the CC chemokine family. 12 Upon sequencing of the entire RANTES gene, seven single nucleotide polymorphisms (SNPs) were identifi...

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Hepatitis C virus infection and mutations of mannose-binding lectin gene MBL

Cited by 70 publications

References 20 publications

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

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

Haplotype-taggingRANTES gene variants influence response to antiviral therapy in chronic hepatitis C

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