Single nucleotide polymorphisms of the mannose-binding lectin are associated with susceptibility to primary biliary cirrhosis

Masanao Matsushita, Hiroshi Miyakawa, Atsushi Tanaka, Minako Hijikata, Kentaro Kikuchi, Hirotoshi Fujikawa, Junya Arai, Shigehiko Sainokami, Kunihiko Hino, Itaru Terai, Shunji Mishiro, M. Eric Gershwin

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38 Scopus citations


Although the immunopathogenesis of primary biliary cirrhosis (PBC) remains unknown, familial clustering of patients with PBC suggests an important role for genetic factors. In addition, recent data support the thesis that the mucosal immune response against intraluminal pathogens may be involved with the onset of PBC. Mannose-binding lectin (MBL) is a key factor in innate mucosal defenses and has several key single nucleotide polymorphisms (SNPs). To study whether MBL gene SNPs are associated with susceptibility to PBC, we studied 65 patients with PBC and 218 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific priming-polymerase chain reaction (SSP-PCR) to examine four polymorphic loci: two (H/L and X/Y) within the promoter region and the other two (P/Q and A/B) within exon-1. We also analyzed serum MBL concentrations. Interestingly, the prevalence of haplotype HYPA, leading to hyper-production of MBL, as well as HYPA/HYPA genotype were significantly increased in PBC compared to controls (0.53 vs. 0.44, P=0.031; 33.9% vs. 17.0%, P=0.003, respectively). Furthermore, individuals homozygous for HYPA had a significantly increased risk for PBC (odds ratio (OR)=2.51, 95% confidence interval (CI)=1.34-4.66). Our results demonstrate that the MBL genotype can be significantly associated with increased risk for PBC, and further, that increased production of MBL plays a critical role in immunopathogenesis.

Original languageEnglish (US)
Pages (from-to)251-257
Number of pages7
JournalJournal of Autoimmunity
Issue number3
StatePublished - Nov 1 2001


  • Innate immune system
  • Mannose-binding lectin (MBL)
  • Primary biliary cirrhosis (PBC)
  • Single nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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