Molecular analysis of HLA-DR beta and DQ beta polymorphism in Chinese with rheumatoid arthritis.
OBJECTIVE
Several studies have suggested that genetic predisposition to rheumatoid arthritis may be related to the presence of specific polymorphic HLA sequences that are often associated with HLA-DR4 haplotypes. This study was performed to determine if an association exists between Chinese with rheumatoid arthritis and a particular HLA-DR beta or DQ beta subtype.


METHODS
This study used the polymerase chain reaction to amplify HLA-DR beta and DQ beta genes, and oligonucleotide probe hybridisation to examine the association of certain polymorphic sequences with rheumatoid arthritis in 23 Chinese patients from Shanghai.


RESULTS
An HLA-DR4 associated sequence was significantly increased in the Chinese patients (43%) compared with healthy controls (14%) from the same location (relative risk = 4.6, 95% confidence limits 1.1 to 19.3). Analysis of the third hyperpolymorphic region of DR4 positive samples was performed to detect polymorphic sequences associated with Dw4, Dw10, Dw13, Dw14, Dw15, and KT2 cellular specificities. Examination of this region showed that 91% of patients had sequences encoding amino acids QRRAA (associated with Dw14 and Dw15) or QKRAA (associated with Dw4) compared with 64% of the DR4 positive controls.


CONCLUSIONS
Rheumatoid arthritis in the Chinese is associated with HLA-DR4. There is a possible relationship between sequences within the third hyperpolymorphic region of the DRB allele and rheumatoid arthritis in the Chinese.
Molkentin
J
J
Blood Center of Southeastern Wisconsin, Milwaukee 53233.
Gregersen
P K
PK
Lin
X
X
Zhu
N
N
Wang
Y
Y
Wang
Y
Y
Chen
S
S
Chen
S
S
Baxter-Lowe
L A
LA
Silver
J
J
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D002681:China; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes