Polymorphism of the 5′ flanking region of the IL-12 receptor β2 gene partially determines the clinical types of leprosy through impaired transcriptional activity

H. Ohyama, K. Ogata, K. Takeuchi, M. Namisato, Y. Fukutomi, F. Nishimura, H. Naruishi, T. Ohira, K. Hashimoto, T. Liu, M. Suzuki, Y. Uemura, S. Matsushita

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)740-743
Number of pages4
JournalJournal of Clinical Pathology
Volume58
Issue number7
DOIs
Publication statusPublished - Jul 1 2005
Externally publishedYes

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Interleukin-12 Receptors
5' Flanking Region
Leprosy
Single Nucleotide Polymorphism
Tuberculoid Leprosy
Haplotypes
Lepromatous Leprosy
Jurkat Cells
Genes
T-Lymphocytes
Reporter Genes
Individuality
Immunogenetics
Interleukin-12
Luciferases
Gene Frequency
Gene Expression
Antigens
Population

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Polymorphism of the 5′ flanking region of the IL-12 receptor β2 gene partially determines the clinical types of leprosy through impaired transcriptional activity. / Ohyama, H.; Ogata, K.; Takeuchi, K.; Namisato, M.; Fukutomi, Y.; Nishimura, F.; Naruishi, H.; Ohira, T.; Hashimoto, K.; Liu, T.; Suzuki, M.; Uemura, Y.; Matsushita, S.

In: Journal of Clinical Pathology, Vol. 58, No. 7, 01.07.2005, p. 740-743.

Research output: Contribution to journalArticle

Ohyama, H, Ogata, K, Takeuchi, K, Namisato, M, Fukutomi, Y, Nishimura, F, Naruishi, H, Ohira, T, Hashimoto, K, Liu, T, Suzuki, M, Uemura, Y & Matsushita, S 2005, 'Polymorphism of the 5′ flanking region of the IL-12 receptor β2 gene partially determines the clinical types of leprosy through impaired transcriptional activity', Journal of Clinical Pathology, vol. 58, no. 7, pp. 740-743. https://doi.org/10.1136/jcp.2004.023903
Ohyama, H. ; Ogata, K. ; Takeuchi, K. ; Namisato, M. ; Fukutomi, Y. ; Nishimura, F. ; Naruishi, H. ; Ohira, T. ; Hashimoto, K. ; Liu, T. ; Suzuki, M. ; Uemura, Y. ; Matsushita, S. / Polymorphism of the 5′ flanking region of the IL-12 receptor β2 gene partially determines the clinical types of leprosy through impaired transcriptional activity. In: Journal of Clinical Pathology. 2005 ; Vol. 58, No. 7. pp. 740-743.
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abstract = "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.",
author = "H. Ohyama and K. Ogata and K. Takeuchi and M. Namisato and Y. Fukutomi and F. Nishimura and H. Naruishi and T. Ohira and K. Hashimoto and T. Liu and M. Suzuki and Y. Uemura and S. Matsushita",
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T1 - Polymorphism of the 5′ flanking region of the IL-12 receptor β2 gene partially determines the clinical types of leprosy through impaired transcriptional activity

AU - Ohyama, H.

AU - Ogata, K.

AU - Takeuchi, K.

AU - Namisato, M.

AU - Fukutomi, Y.

AU - Nishimura, F.

AU - Naruishi, H.

AU - Ohira, T.

AU - Hashimoto, K.

AU - Liu, T.

AU - Suzuki, M.

AU - Uemura, Y.

AU - Matsushita, S.

PY - 2005/7/1

Y1 - 2005/7/1

N2 - 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.

AB - 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.

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