Extended report
Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*,
and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis
F Castroa, E Acevedob, E Ciusani* c, J A Anguloa, F A Wollheimd, M Sandberg-Wollheimc
a Hospital Central
FAP, Lima, Peru, b G Almenara Hospital ESSALUD, Lima, Peru, c Department of Neurology,
University Hospital, S-221 85 Lund, Sweden, d Department
of Rheumatology, University Hospital, Lund
Correspondence to: Dr M Sandberg-Wollheim Magnhild.Sandberg-Wollheim{at}neurol.lu.se
Accepted for publication 15 December
2000
OBJECTIVE
To study the
association between rheumatoid arthritis (RA) and HLA and tumour
necrosis factor (TNF) polymorphism in Peruvian mestizo patients in
comparison with ethnically similar controls.
METHODSSeventy nine
patients with RA and 65 ethnically matched healthy controls were
genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNF
and TNF
alleles using PCR amplification. Clinical severity was assessed as
mild, moderate, or severe in 35 of the patients.
RESULTSTNF6
showed the strongest association with disease susceptibility. The
TNF6 allele was more common in patients than in controls (p<0.0076)
and the proportion of patients with at least one copy of this allele
was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles
with the shared epitope sequence, only the DRB1*1402 allele was
significantly increased in patients compared with controls (p<0.0311),
as was the proportion of patients with at least one copy of this allele
(p<0.0232, relative risk 2.74). In contrast, the overall frequency of
alleles with the shared epitope was not different in patients and
controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was
significantly more common in patients. TNF6 was more common in
patients whether or not they had this haplotype. None of the 11 patients lacking the TNF6 allele had severe disease.
CONCLUSIONSThis study
shows for the first time that TNF gene polymorphism is associated with
susceptibility to RA in a non-white population. TNF6 and
HLA-DRB1*1402 independently conferred significantly increased risk in
Peruvian mestizo patients.
* Present address: Istituto Nationale Neurologico "Carlo Besta", Milano, Italy
© 2001 by Annals of the Rheumatic Diseases
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