Investigation of the MHC2TA gene, associated with rheumatoid arthritis in a Swedish population, in a UK rheumatoid arthritis cohort.
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.


CONCLUSIONS
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.
Eyre
Stephen
S
University of Manchester, Manchester, UK. Stephen.Eyre@manchester.ac.uk
Bowes
John
J
Spreckley
Kristian
K
Potter
Catherine
C
Ring
Susan
S
Strachan
David
D
Worthington
Jane
J
Barton
Anne
A
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D013548:Sweden; D015534:Trans-Activators / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators