Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations.
OBJECTIVE
Recent studies have identified a number of novel rheumatoid arthritis (RA) susceptibility loci in Caucasian populations. The aim of this study was to determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40 identified in Caucasians are also associated with RA in a Korean case-control collection. We also comprehensively evaluated the genetic variation within PTPN22, a well-established autoimmune disease-associated gene.


METHODS
We designed an experiment to thoroughly evaluate the PTPN22 linkage disequilibrium region, using tag single-nucleotide polymorphisms (SNPs) and disease-associated SNPs at 5 RA-associated loci recently identified in Caucasians, in 1,128 Korean patients with RA and 1,022 ethnically matched control subjects. We also resequenced the PTPN22 gene to seek novel coding variants that might be contributing to disease in this population.


RESULTS
None of the susceptibility loci identified in Caucasian patients with RA contributed significantly to disease in Koreans. Although tag SNPs covering the PTPN22 linkage disequilibrium block were polymorphic, they did not reveal any disease association, and resequencing did not identify any new common coding region variants in this population. The 6q23 and 4q27 SNPs assayed were nonpolymorphic in this population, and the TRAF1/C5, CD40, and CCL21 SNPs did not show any evidence for association with RA in this population of Korean patients.


CONCLUSIONS
The genetic risk factors for RA are different in Caucasian and Korean patients. Although patients of different ethnic groups share the HLA region as a major genetic risk locus, most other genes shown to be significantly associated with disease in Caucasians appear not to play a role in Korean patients with RA.
Lee
Hye-Soon
HS
Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Seoul, South Korea.
Korman
Benjamin D
BD
Le
Julie M
JM
Kastner
Daniel L
DL
Remmers
Elaine F
EF
Gregersen
Peter K
PK
Bae
Sang-Cheol
SC
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000208:ethnology / Q000235:genetics*
C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22