Eyre SS, Bowes J, Spreckley KB, Potter C, Ring S, Strachan D, Worthington J, Barton
Arthritis Rheum. 2006;54( 11):3417-22.
OBJECTIVE: A recent study of rheumatoid arthritis (RA) showed an association with
a functional single-nucleotide polymorphism (SNP) mapping to the promoter region of
the MHC2TA gene on chromosome 16p13 in a Swedish population. Interestingly, evidence
for linkage to this region has been detected previously in a subgroup of UK RA families
carrying 2 copies of shared epitope (SE) alleles. Therefore, we undertook this study
to investigate the association of the MHC2TA gene promoter with RA in a UK Caucasian
population. METHODS: Association with 5 SNPs spanning the promoter region of the MHC2TA
gene was investigated in 813 UK RA patients and 532 population controls. Association
with a functional putative RA-causal polymorphism (-168*G/A [rs3087456]) was tested
in a total of 1,401 UK RA patients and 2,475 controls. Genotyping was performed using
a Sequenom MassArray platform. Estimated haplotype frequencies were generated using
the expectation-maximization algorithm and compared between patients and controls.
RESULTS: All SNPs were in Hardy-Weinberg equilibrium. No evidence for association
was found, either with the putative RA-causal polymorphism (-168*G/A) or with the
other SNPs tested. Haplotype analysis revealed extensive linkage disequilibrium across
the promoter region but no evidence for association. Stratifying the data set by carriage
of SE alleles did not alter the conclusions. CONCLUSION: A functional polymorphism
of the MHC2TA gene locus previously associated with RA in a European population has
not been associated with RA in a UK population. These findings do not provide support
for the notion that this gene plays a major role in the etiology of RA.