JCP

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
[Advanced]

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Add article to my folders
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ohyama, H
Right arrow Articles by Matsushita, S
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ohyama, H
Right arrow Articles by Matsushita, S
Journal of Clinical Pathology 2005;58:740-743
© 2005 BMJ Publishing Group Ltd & Association of Clinical Pathologists


ORIGINAL ARTICLE

Polymorphism of the 5' flanking region of the IL-12 receptor ß2 gene partially determines the clinical types of leprosy through impaired transcriptional activity

H Ohyama1, K Ogata2, K Takeuchi3, M Namisato4, Y Fukutomi5, F Nishimura3, H Naruishi3, T Ohira3, K Hashimoto1, T Liu1, M Suzuki1, Y Uemura1, S Matsushita1

1 Department of Allergy and Immunology, Saitama Medical School, Moroyama 350-0495, Japan
2 Life Science Laboratory, Shimadzu Corporation, Kyoto 604-8511, Japan
3 Department of Patho-physiology/Periodontal Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8525, Japan
4 National Sanatorium Kuryu-Rakusenen, Kusatsu 377-1711, Japan
5 Leprosy Research Centre, National Institute of Infectious Disease, Higashi-murayama 189-0002, Japan

Correspondence to:
Dr H Ohyama
First Department of Pathology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan; ohyama{at}hyo-med.ac.jp Background: Individual differences in T cell responsiveness to interleukin 12 (IL-12), resulting from inherited factors, may be responsible for differences in the intensity of cell mediated immune (CMI) responses in patients with leprosy, a disease with a wide clinical spectrum.

Aim: Polymorphisms in the 5' flanking region of the IL12RB2 gene were analysed to determine potential immunogenetic factors affecting CMI responses, using leprosy as a model.

Methods: Polymorphisms in the 5' flanking region of IL12RB2 were examined using direct sequencing techniques, and allele frequencies between patients with lepromatous leprosy and patients with tuberculoid leprosy were compared. The effect of these single nucleotide polymorphisms (SNPs) on IL12RB2 expression was estimated using the dual luciferase reporter gene assay in Jurkat T cells.

Results: Several SNPs, including –1035A>G, –1023A>G, –650delG, and –465A>G, were detected within the 5' flanking region of IL12RB2. The frequency of haplotype 1 (–1035A, –1023A, –650G, –464A) was high in the general Japanese population, but was significantly lower in lepromatous patients compared with tuberculoid patients and healthy controls. Reporter gene assays using Jurkat T cells revealed that all haplotypes carrying one or more SNP exhibited a lower transcriptional activity compared with haplotype 1.

Conclusion: SNPs within the 5' flanking region of IL12RB2 affect the degree of expression of this gene and may be implicated in individual differences in CMI responsiveness to mycobacterial antigens, leading to lepromatous or tuberculoid leprosy.


Abbreviations: CMI, cell mediated immunity; IL-12, interleukin 12; IL-12R, interleukin 12 receptor; L-lep, lepromatous leprosy; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism; Th, T helper; T-lep, tuberculoid type leprosy

Keywords: single nucleotide polymorphisms; IL12RB2; cell mediated immune responses; leprosy; mycobacterial antigens







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
Journal of Clinical Pathology Molecular Pathology
Terms and conditions relating to subscriptions purchased online  ¦  Website terms and conditions  ¦  Privacy policy
Copyright © 2005 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.