Cyclooxygenase-2 polymorphisms and risk of rheumatoid arthritis in Koreans.
OBJECTIVE
To determine the association of single-nucleotide polymorphisms (SNP) in the cyclooxygenase-2 (COX-2) gene with the risk and radiologic severity of rheumatoid arthritis (RA) in Koreans.


METHODS
Sequencing of the COX-2 gene using a DNA analyzer revealed genetic variants in 24 Korean DNA samples. A total of 1201 Korean patients with RA and 973 controls were genotyped using the TaqMan method. HLA-DRB1 was genotyped by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization techniques. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) and the corresponding probability values for each SNP site and haplotype.


RESULTS
Direct sequencing identified 23 SNP of COX-2 gene, from which 2 common SNP (-1329A-->G and 6365T-->C) were selected based on the linkage disequilibrium status among SNP and minor allele frequencies. The -899G-->C SNP was also studied because it is reportedly associated with the risk of RA. The -1329A-->G SNP was not significantly associated with the risk of RA. However, the risk of RA was significantly lower in the presence of the C allele for 6365T-->C (OR 0.50, 95% CI 0.29-0.85, in a recessive model, and OR 0.80, 95% CI 0.67-0.97, in a codominant model). The C allele for -899G-->C was also associated with a significantly lower risk of RA (OR 0.67, 95% CI 0.48-0.95, in a codominant model). The radiologic severity of RA was not associated with COX-2 polymorphisms.


CONCLUSIONS
Our study revealed a possible protective influence of the C allele for 6365T-->C and for -899G-->C in RA.
Yun
Hye-Ryeon
HR
Division of Rheumatology, Department of Internal Medicine, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea.
Lee
Soo-Ok
SO
Choi
Eun Ju
EJ
Shin
Hyoung Doo
HD
Jun
Jae-Bum
JB
Bae
Sang-Cheol
SC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007723:Korea; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011859:Radiography; D012307:Risk Factors; D012720:Severity of Illness Index
D051546:Cyclooxygenase 2