Genetic polymorphisms of tumour necrosis factor receptor superfamily 1A and 1B affect responses to infliximab in Japanese patients with Crohn's disease.
BACKGROUND
Tumour necrosis factor alpha is the key inflammatory cytokine involved in the pathogenesis of Crohn's disease. Infliximab, a chimaeric monoclonal antibody of tumour necrosis factor-alpha is successfully used for the treatment of Crohn's disease, although the response to infliximab therapy differs among patients. The genetic background of the individual may partially explain the differences of the responsiveness.


OBJECTIVE
To investigate whether the polymorphisms in these genes are associated with the response to infliximab treatment as tumour necrosis factor-alpha exerts its biological activity through TNF receptor superfamily 1A and 1B.


METHODS
Eighty Crohn's disease patients were enrolled in the study and classified into responder and nonresponder according to the efficacy of infliximab treatment. Single nucleotide polymorphisms of TNF receptor superfamily 1A (rs767455 and rs4149570) and TNF receptor superfamily 1B (rs1061622, rs1061624 and rs3397) were determined.


RESULTS
The minor allele carrier of rs767455 showed a significant association with a lack of efficacy compared to the major genotype (OR = 0.26; 95% CI: 0.08-0.91). A TNF receptor superfamily 1B haplotype inferred by rs1061624 and rs3397 also showed significant differences in the distribution between responder and nonresponder (P = 0.01).


CONCLUSIONS
These results suggest that tumour necrosis factor receptor genotypes may be involved in the different responses to infliximab in Japanese patients with Crohn's disease.
Matsukura
H
H
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Ikeda
S
S
Yoshimura
N
N
Takazoe
M
M
Muramatsu
M
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000069285:Infliximab; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D012044:Regression Analysis
D000911:Antibodies, Monoclonal; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D000069285:Infliximab