Association of IL12RB1 polymorphisms with susceptibility to and severity of tuberculosis in Japanese: a gene-based association analysis of 21 candidate genes.
Tuberculosis (TB) is the second commonest cause of death from infectious disease after HIV/AIDS worldwide. Association studies have revealed that host genetic factors, such as human leukocyte antigen and solute carrier family 11 member A1 (NRAMP1), play roles in susceptibility to TB. To identify host genetic factors involved in the susceptibility to TB in Japanese, we performed a gene-based association analysis of 21 candidate genes on 87 TB patients and 265 controls using marker single nucleotide polymorphisms (SNPs). For the genes with two or more marker SNPs exhibiting significant allele association, we subsequently analysed the association between adjacent coding SNPs (cSNPs) and TB. Among a total of 118 marker SNPs, 3 of IL1B and 2 of IL12RB1 showed association with TB. Non-synomymous cSNPs were not identified in IL1B. Association studies on four non-synomymous cSNPs of IL12RB1 (641A/G, 1094T/C, 1132C/G, 1573G/A) in linkage disequilibrium showed that three of them (641A/G, 1094T/C, 1132C/G) were significantly associated with the development of TB. Haplotype analysis on the four cSNPs demonstrated that frequency of ATGG haplotype was significantly lower in TB patients than in controls. When TB patients were divided into two subgroups according to the severity of lung disease, advanced subgroup showed a prominent association with 641A/G, 1094T/C and 1132C/G SNPs. These data suggested that genetic variants of IL12RB1, at least in part, confer genetic susceptibility to TB, and are associated with the progression of the disease, in Japanese.
Kusuhara
K
K
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. kkusuhar@pediatr.med.kyushu-u.ac.jp
Yamamoto
K
K
Okada
K
K
Mizuno
Y
Y
Hara
T
T
D000368:Aged; D044466:Asian People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
C508438:IL12RB1 protein, human; D053707:Receptors, Interleukin-12