Abstract
Interleukin-12 receptor beta 1 (IL12RB1), interleukin-12 receptor beta 2 (IL12RB2), and interferon gamma receptor 1 (IFNGR1) perform important roles in the host defense against intracellular pathogens such as Mycobacteria. Several mutations within their genes have been confirmed as associated with increased susceptibility to mycobacterial infection. However, the association between mutations of the IL12RB1, IL12RB2, and IFNGR1 encoding genes and lepromatous leprosy has not been studied. This study screened for polymorphisms within IL12RB1, IL12RB2, and IFNGR1 encoding genes in the Korean populations using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) DNA sequencing assay, and an association study was performed using the missense mutations of 705 A/G (Q214R), 1196 G/C (G378R), 1637 G/A (A525T), and 1664 C/T (P534S) of the IL12RB1, 83 G/A (V14M), and 1443 T/C (L467P) for the IFNGR1 encoding genes. There were no differences in the genotype and allele frequencies of IL12RB1 and IFNGR1 genes between 93 lepromatous leprosy patients and 94 control subjects. In conclusion, missense mutations of 705 A/G (Q214R), 1196 G/C (G378R), 1637 G/A (A525T), 1664 C/T (P534S) of the IL12RB1, 83 G/A (V14 M), and 1443 T/C (L467P) of the IFNGR1 encoding genes have no association with the susceptibility to lepromatous leprosy in the Korean population.
References
Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, Drysdale P, Jouanguy E, Doffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL (1998a) Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280:1432–1435
Altare F, Jouanguy E, Lamhamedi-Cherradi S, Fondaneche MC, Fizame C, Ribierre F, Merlin G, Dembic Z, Schreiber R, Lisowska-Grospierre B, Fischer A, Seboun E, Casanova JL (1998b) A causative relationship between mutant IFNgR1 alleles and impaired cellular response to IFNgamma in a compound heterozygous child. Am J Hum Genet 62:723–726
Bach EA, Aguet M, Schreiber RD (1997) The IFN gamma receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol 15:563–591
De Jong R, Altare F, Haagen IA, Elferink DG, Boer T, van Breda Vriesman PJ, Kabel PJ, Draaisma JM, van Dissel JT, Kroon FP, Casanova JL, Ottenhoff TH (1998) Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280:1435–1438
Dorman SE, Holland SM (1998) Mutation in the signal-transducing chain of the interferon-gamma receptor and susceptibility to mycobacterial infection. J Clin Invest 101:2364–2369
Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, Presky DH (1998) The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol 16:495–521
Holland SM, Dorman SE, Kwon A, Pitha-Rowe IF, Frucht DM, Gerstberger SM, Noel GJ, Vesterhus P, Brown MR, Fleisher TA (1998) Abnormal regulation of interferon-gamma, interleukin-12, and tumor necrosis factor-alpha in human interferon-gamma receptor 1 deficiency. J Infect Dis 178:1095–1104
Jouanguy E, Lamhamedi-Cherradi S, Altare F, Fondaneche MC, Tuerlinckx D, Blanche S, Emile JF, Gaillard JL, Schreiber R, Levin M, Fischer A, Hivroz C, Casanova JL (1997) Partial interferon-gamma receptor 1 deficiency in a child with tuberculoid bacillus Calmette-Guerin infection and a sibling with clinical tuberculosis. J Clin Invest 100:2658–2664
Jouanguy E, Lamhamedi-Cherradi S, Lammas D, Dorman SE, Fondaneche MC, Dupuis S, Doffinger R, Altare F, Girdlestone J, Emile JF, Ducoulombier H, Edgar D, Clarke J, Oxelius VA, Brai M, Novelli V, Heyne K, Fischer A, Holland SM, Kumararatne DS, Schreiber RD, Casanova JL (1999) A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet 21:370–378
Kang TJ, Chae GT (2001) Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol 31:53–58
Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, Levin M (1996) A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 335:1941–1949
Pierre-Audigier C, Jouanguy E, Lamhamedi S, Altare F, Rauzier J, Vincent V, Canioni D, Emile JF, Fischer A, Blanche S, Gaillard JL, Casanova JL (1997) Fatal disseminated Mycobacterium smegmatis infection in a child with inherited interferon gamma receptor deficiency. Clin Infect Dis 24:982–984
Ridley DS, Jopling WH (1966) Classification of leprosy according to immunity: a five-group system. Int J Lepr 34:255–273
Sakai T, Matsuoka M, Aoki M, Nosaka K, Mitsuya H (2001) Missense mutation of the interleukin-12 receptor beta1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection. Blood 97:2688–2694
Santos AR, Suffys PN, Vanderborght PR, Moraes MO, Vieira LMM, Cabello PH, Bakker AM, Matos HJ, Huizinga TWJ, Ottenhoff THM, Sampaio EP, Sarno EN (2002) Role of tumor necrosis factor-alpha and interleukin-10 promoter gene polymorphisms in leprosy. J Infect Dis 186:1687–1691
Tanaka Y, Nakashima H, Hisano C, Kohsaka T, Nemoto Y, Niiro H, Otsuka T, Otsuka T, Imamura T, Niho Y (1999) Association of the interferon-gamma receptor variant (Val14Met) with systemic lupus erythematosus. Immunogenetics 49:266–271
Wibawa T, Soebono H, Matsuo M (2002) Association of a missense mutation of the laminin a2 gene with tuberculoid type of leprosy in Indonesian patients. Trop Med Int Health 7:631–636
Author information
Authors and Affiliations
Corresponding author
Additional information
S.B. Lee and B.C. Kim contributed equally to this work.
The new polymorphism data reported in this paper have been submitted to the HGBASE database and have been assigned the accession numbers SNP001745639 for 451 G/A of IL12RB1, SNP001745640 for 91 G/A of IFNGR1, and SNP001745641 for 1664 C/T of IL12RB1.
Rights and permissions
About this article
Cite this article
Lee, SB., Kim, B.C., Jin, S.H. et al. Missense mutations of the interleukin-12 receptor beta 1(IL12RB1) and interferon-gamma receptor 1 (IFNGR1) genes are not associated with susceptibility to lepromatous leprosy in Korea. Immunogenetics 55, 177–181 (2003). https://doi.org/10.1007/s00251-003-0573-x
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-003-0573-x