TAP2D is associated with HLA-B44 and DR4 and may contribute to rheumatoid arthritis and Felty's syndrome susceptibility.
OBJECTIVE
TAP2 transporter gene polymorphisms have been ascertained in patients with rheumatoid arthritis (RA) and Felty's syndrome (FS) to determine whether particular alleles of this gene are disease associated.


METHODS
TAP2 dimorphisms at amino acid positions 379, 565 and 665 were detected using ARMS-PCR in 89 RA patients, 24 FS patients and 64 control subjects. TAP 2 alleles were assigned from these results.


RESULTS
The frequency of one particular allele, TAP2D, was increased in both RA (OR 2.6, 95% CI 1.2 - 5.8) and FS (OR 3.9, 95% CI 1.4 - 10.7). When individual amino acid polymorphisms were compared between patients and controls, isoleucine at position 379 (present in TAP2D and TAP2C) was significantly increased, indicating that this dimorphism itself may be associated with RA (OR 5.0, 95% CI 2.4 - 10.2) and FS (OR 5.0, 95% CI 1.91 - 3.2).


CONCLUSIONS
The presence of TAP2D was greatly increased in HLA-B44/DR4 positive RA (83%) and FS (67%) patients. These frequencies were appreciably higher than in the HLA-B44/DR4 controls (11%), suggesting that linkage disequilibrium alone may not explain the increase in TAP2D frequency in patients and that this allele may represent an additional risk factor in these conditions.
Hillarby
M C
MC
ARC Epidemiology Research Unit, University of Manchester, U.K.
Davies
E J
EJ
Donn
R P
RP
Grennan
D M
DM
Ollier
W E
WE
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000596:Amino Acids / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000032:analysis; D005258:Felty Syndrome / Q000235:genetics* / Q000378:metabolism; D015235:HLA-B Antigens / Q000235:genetics*; D059948:HLA-B44 Antigen; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000596:Amino Acids; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D015804:HLA-DR4 Antigen; C071692:TAP2 protein, human; D004247:DNA