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

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.

Lack of an Association between Interleukin-12 Receptor β1 Polymorphisms and Tuberculosis in Koreans

“…DNA was extracted using a Puregene DNA Isolation Kit (Gentra Systems, Minneapolis, Minn., USA) following the manufacturer’s protocol. We typed for 5 previously reported SNPs that cause missense mutations in the coding sequence of the IL-12 receptor β1 gene in Koreans [20], namely +705A/G (Q214R, NCBI SNP ID:rs 11575934), +1158T/C (M365T, NCBI SNP ID:rs 375947), +1196G/C (G378R, NCBI SNP ID:rs 401502), +1637G/A (A525T, NCBI SNP ID:rs 11575935) and +1664 C/T (P534S, HGBASE database ID:SNP001745641). For +705A/G genotyping, genomic DNA was amplified using the primer set 5′-ggttaagtgactggtgccaag-3′ and 5′-ctcaaaccactggcctcaag-3′.…”

“…Moreover, polymorphisms in the coding sequence of the IL-12 receptor gene have been reported to be associated with tuberculosis in the Japanese and Moroccan populations [18, 19], but not with leprosy in Koreans [20]. In this study, we examined whether single nucleotide polymorphisms (SNPs) in IL-12 receptor β1 gene are associated with TB in Koreans.…”

Role ofHLA,KIR,MICA, and Cytokines Genes in Leprosy

“…However, in Korean patients, Lee et al [59] found no significant differences in allele frequencies of IL12RB1 between leprosy patients and the control group [59]. Now, in relation to gene in the 5′ flanking region of IL12RB2 , Ohyama et al [60] determined the functional effects of these SNPs on NK-cell activity, including IFN- γ production and IL-12RB2 gene expression.…”

“…In Korean patients, no significant differences were found in allele frequencies IFNGR1 (interferon γ receptor 1) between leprosy patients and the control group [59]. However, a case report showed that the IFNGR1 polymorphism at position −56T/C was positively associated with an increased susceptibility to leprosy, in Iranian children of the same family [68].…”

Interferon-Gamma Receptor-1 Gene Promoter Polymorphisms and Susceptibility to Leprosy in Children of a Single Family

“…Few investigators showed an association between mutation of IFNGR1 and lepromatous leprosy patient, but others did not support the idea. 10,12 Generally, the diverse genetic results of the disease acquisition might be explained by distinct genetic susceptibly to the disease among different populations. 2 Clearly, the complete absence of IFNGR1 on cell surface induces so profound an immune defect that such mutations are unlikely to explain M. leprae susceptibility in the general population.…”