Polymorphism of HLA-DR and HLA-DQ in rheumatoid arthritis patients and clinical response to methotrexate--a hospital-based study.
OBJECTIVE
To investigate the frequency and distribution of DRB1 and DQB1 alleles in Patients with rheumatoid arthritis (RA) and analyze the relationship between clinical response to methotrexate (MTX) and the HLA-DR and HLA-DQ genotypes in these patients.


METHODS
In this case-control study, the HLA-DRB1 and HLA-DQB1 polymorphism in 91 RA patients and 91 healthy controls was done using polymerase chain reaction and sequence specific primers.


RESULTS
There was no statistical difference in frequencies of HLA-DRB1*03, DRB1*04, DRB1*07, DRB1*10, DRB1*11, DRB1*12, DRB1*13, DRB1*14, DRB1*15 and DRB1*16 genotypes between patients and controls. However, DRB1*01 was found to be significantly more common (p=0.015) in RA patients compared to controls. HLA-DRB1*15 was more common in patients (43.5%) compared to controls (30.8%) but results were not significant. HLA-DRB1*08 and DRB1*09 were present in negligible number in patients as well as controls while HLA-DRB1*12 was conspicuously absent in controls. Similarly, DQB1*06 was also significantly more common (p = 0.01) among the patients compared to healthy control subjects, while there was no statistical difference in the frequencies of DQB1*02, DQB1*03, DQB1*04 and DQB1*05 among the cases and the controls. RA susceptibility in most patients appeared to be associated with the HLA-DRB1*01/DQB1 *06 genotype. Regarding association between HLA-DR or HLA-DQ genotype and clinical response to methotrexate (MTX), the data showed that with the exception of HLA-DRB1*03, there appears to be no association between the particular subtypes of HLA-DR and HLA-DQ. HLA-DRB1*03 was significantly-more common among non-responders to MTX alluding to the possibility that another genes responsible for MTX metabolism, might be in linkage disequilibrium with HLA-DRB1*03 in the Pakistani population, thereby making such individuals non-responsive to MTX-therapy.


CONCLUSIONS
RA susceptibility in most Pakistani patients is associated with the HLA-DRB1*01/DQB1*06 genotype. HLA-DRB1*03 was found to be significantly more common among non-responders to MTX treatment suggesting that Pakistani patients with this genotype are less likely to benefit from MTX.
Ali
Azra Arif I
AA
Department of Biological and Biomedical Sciences3, Aga Khan University, Karachi.
Moatter
Tariq
T
Baig
Jawed Altaf
JA
Iqbal
Ahmed
A
Hussain
Azmat
A
Iqbal
Mohammad Perwaiz
MP
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010154:Pakistan; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D015415:Biomarkers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D008727:Methotrexate