CYP1A2 genotype and rheumatoid arthritis in Koreans.

Cytochrome P540 (CYP) 1A2 plays a role in the production of reactive oxygen species (ROS), which have been implicated in the development of rheumatoid arthritis (RA). The objective of this study was to investigate the association between a common polymorphism in the CYP1A2 gene with risk and severity of RA in a Korean population. Cases (n = 1321) with RA and controls (n = 1037) were genotyped for the CYP1A2 -163 A>C polymorphism by real-time PCR. HLA-DRB1 typing and further subtyping of all alleles was performed by PCR, sequence-specific oligonucleotide probe hybridization and direct DNA sequencing analysis. The odds ratio (OR) [(95% confidence interval (CI)] of RA associated with the low inducible C allele was 1.11 (0.80-1.55) among non-shared epitope (SE) carriers, 0.82 (0.56-1.20) among heterozygotes and 0.32 (0.10-1.04) among individuals homozygous for the SE (P = 0.03 for CYP1A2-SE interaction). A protective effect of the low inducibility CYP1A2 C allele among carriers of the SE suggests that a product of CYP1A2-mediated metabolism, such as ROS, may be involved in the development of RA.