Immunogenetic analysis of silicosis in Japan.
We previously reported that a gene in linkage disequilibrium with HLA-Bw54, DR4, and DRw53 might control the susceptibility to silicosis (K. Honda et al. 1988. N. Engl. J. Med. 319:1610). To further define the HLA-linked gene and other genetic factors for predisposition of silicosis, we determined for HLA-DQ and DP alleles using the polymerase chain reaction and sequence-specific oligonucleotide probes and made a restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes, immunoglobulin lambda variable chain (IGLV) gene, and T-cell receptor alpha and beta genes in 46 Japanese patients with silicosis. The frequency of DQB1*0401 (relative risk [RR] = 2.2, P < 0.02) was increased and that of DQB1*0601 (RR = 0.36, P < 0.01) was decreased in the patients. RFLP analysis of C4 and IGLV genes showed significant association between silicosis and a specific RFLP pattern of C4A3-C4B5 allotype (RR = 2.3, P < 0.05) and that of IGLV 5.3 kb (RR = 0.33, P < 0.003). No other genetic markers showed significant association. Statistical analyses of the associated genetic markers revealed that the HLA-Bw54 was the allele that showed primary association with silicosis and the frequencies of the C4 and HLA-DQ alleles were suggested to be increased due to their linkage disequilibrium with the HLA-Bw54. We conclude that the major gene for silicosis may be mapped near the HLA-B locus.
Honda
K
K
Department of Genetics, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kimura
A
A
Dong
R P
RP
Tamai
H
H
Nagato
H
H
Nishimura
Y
Y
Sasazuki
T
T
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005803:Genes, Immunoglobulin; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D005819:Genetic Markers; D015235:HLA-B Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D007564:Japan; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012829:Silicosis / Q000235:genetics*
D005819:Genetic Markers; D015235:HLA-B Antigens; D006681:HLA-D Antigens; D007146:Immunoglobulin lambda-Chains; D011948:Receptors, Antigen, T-Cell