Genetic analysis of TAP2 in systemic lupus erythematosus patients from two ethnic groups.
The aim of this study was to determine whether the TAP2 (Transporter associated with Antigen Processing 2) locus is involved in susceptibility to systemic lupus erythematosus (SLE). We adopted the interethnic approach to overcome problems in the analysis resulting from linkage disequilibrium. The TAP2 gene polymorphisms of the codons corresponding to amino acid positions 379, 565 and 665 were investigated by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in 186 patients (151 white Europeans, 35 Afrocaribbeans) and 183 controls (79 white Europeans, 104 Afrocaribbeans). In the European SLE patients, the frequency of the TAP2 type V-A-TA was marginally lower compared with the control group (31% vs 42%), with negative linkage disequilibrium between this TAP2 type and DR3 probably accounting for the difference. For the European SLE patients, we confirmed a significant association of DR3 with disease status [odds ratio = 4.16, 95% confidence interval (CI), 2.08-8.39] and in the patients with DR3 there was a significantly high frequency of the TAP2 type V-A-T-. In the Afrocaribbean SLE patients, any associations of disease status with TAP2 phenotype were the inverse of those in the European patients. Thus, in these patients the frequency of V-A-TA was higher than in controls (46% vs 26%, OR = 2.4, 95% CI 1.01-5.74), while the frequency of V-A-T- was lower (26% vs 40%, not significant). Despite possible sampling error, the lack of a difference in TAP2 status between cases and controls within ethnic groups and, if anything, an inverse association across ethnic groups, makes it unlikely that the TAP2 polymorphism studied here is of primary relevance to SLE susceptibility.