Polymorphism of TAP1 and TAP2 in Japanese patients with rheumatoid arthritis

Takeuchi, Fujio; Nakano, Ken; Matsuta, Kunio; Takizawa, Kenji; Nabeta, Hiromi; Kuwata, Shoji; Ito, Kenichiro

doi:10.1111/j.1399-0039.1997.tb02753.x

Cited by 15 publications

(6 citation statements)

References 9 publications

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“…The LD block to which HLA–DQB2 belongs also contains the TAP1/TAP2 genes, which function in the delivery of peptides to the endoplasmic reticulum for the assembly of class I MHC molecules and the HLA–DMA/DMB genes, which play a central role in the peptide loading of class II MHC molecules. The association of polymorphism in these genes with RA has been investigated in several studies, and no statistically significant association has been observed (37–39). In our study, several SNPs in the TAP2 and HLA–DMB genes were genotyped, but no significant associations were observed in the DRB1‐conditioned analysis (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Analysis of single‐nucleotide polymorphisms in Japanese rheumatoid arthritis patients shows additional susceptibility markers besides the classic shared epitope susceptibility sequences

Kochi¹,

Yamada²,

Kobayashi³

et al. 2004

Arthritis & Rheumatism

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Objective. To examine the entire HLA region for loci (other than the DRB1 locus) associated with rheumatoid arthritis (RA) susceptibility, by typing HLA-DRB1 alleles and multiple single-nucleotide polymorphisms (SNPs) in the Japanese population.Methods. The HLA-DRB1 alleles and 88 SNPs distributed over the HLA gene complex were genotyped, for 828 patients with RA and 1,032 control subjects. The data were evaluated for linkage disequilibrium, and case-control associations were analyzed in 2 ways, in the presence or absence of the disease-susceptibility DRB1 allele, to detect loci independent of the DRB1 allele.Results. HLA-DRB1 alleles *0405, *0401, *0901, *0101, *1401, *1602, *0403, and *1405 were significantly associated with RA in the Japanese population. The smallest P value (P ‫؍‬ 1.4 ؋ 10 ؊27 ) was observed in association with an intronic SNP of the NOTCH4 gene, which was due to strong linkage disequilibrium with the HLA-DRB1 allele. A strong association that was independent of HLA-DRB1 shared epitope alleles was observed in 2 SNPs: one in the intron of the MICA gene, the other in the intron of the HLA-DQB2 gene. Their association with RA, independent of HLA-DRB1 shared epitope alleles, was suggestive (P ‫؍‬ 0.0024 [corrected P (P corr ) ‫؍‬ 0.068, and P ‫؍‬ 0.00037 [P corr ‫؍‬ 0.012], respectively).Conclusion. These findings suggest that 1 or more other loci besides the HLA-DRB1 or other DRB1 (nonshared epitope, non-*0901) alleles are involved in RA susceptibility/protection.

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Section: Discussionmentioning

confidence: 99%

Analysis of single‐nucleotide polymorphisms in Japanese rheumatoid arthritis patients shows additional susceptibility markers besides the classic shared epitope susceptibility sequences

Kochi¹,

Yamada²,

Kobayashi³

et al. 2004

Arthritis & Rheumatism

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“…The association of TAP1 and TAP2 gene polymorphisms with RA has been studied in various countries, with conflicting results (Wordsworth et al ., 1993; Marsal et al ., 1994; Singal & Qiu, 1994; Vandevyver et al ., 1995; Hillarby et al ., 1996; Takeuchi et al ., 1997; Tuokko et al ., 1998; Vinasco et al ., 1998; Vejbaesya et al ., 2000). However, all known TAP1 and TAP2 polymorphisms were not systematically investigated in these studies.…”

Section: Introductionmentioning

confidence: 99%

TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France

Zhang

Chabod²,

Penfornis³

et al. 2002

European Journal of Immunogenetics

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The 'transporter associated with antigen processing' (TAP) gene products are involved in the processing of endogenous peptides that bind to class I molecules. Polymorphism within these genes could alter the level of the immune response, a phenomenon relevant to the development of autoimmune diseases. In this study, we examined the polymorphism of TAP1 and TAP2 genes in patients with rheumatoid arthritis (RA). TAP1 and TAP2 typing was performed for 138 Caucasian RA patients and 100 healthy controls, all originating from eastern France. TAP1 polymorphic residues at positions 333 and 637 and amino acid variants 379, 565, 651 and 665 in the TAP2 gene were found using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). This method enabled us to determine four TAP1 alleles (TAP1A to TAP1D) and eight TAP2 alleles (TAP2A to TAP2H). All patients and controls had been HLA-DRB1* genotyped. The polymorphic residues TAP1333 and TAP1637 did not show any difference in their distribution between patients and controls. Similar findings were obtained for TAP2379 and TAP2665. However, we found an increased frequency of Thr homozygosity and heterozygosity at position 565 in the TAP2 gene in RA patients (RA vs. controls: 25.3 vs. 14%; P = 0.032; OR = 2.09; CI = 1.01-4.38). Similarly, the prevalence of subjects who were homozygote and heterozygote for Cys651 was increased in the RA group (RA vs. controls: 36.8 vs. 11%; P = 0.02). The dimorphic site TAP2565 defines TAP2D and TAP2E alleles, while the site at position 651 characterizes TAP2F. Thus, we found that TAP2D and TAP2E alleles were more prevalent in RA, but not significantly so (RA vs. controls: TAP2D: 10 vs. 3.6%; P = 0.24; TAP2E: 3.6 vs. 0%; P = 0.19). Similarly, the frequency of TAP2F was higher in RA patients (24.5%) than in controls (11.3%), but this was not significant after correction (P = 0.029; Pcorr = 0.17). Finally, we found no linkage disequilibrium between DRB1* RA-associated alleles and amino acid substitution Thr565 or TAP2D and TAP2E alleles, whereas Cys651 (and TAP2F) was not independent of DRB1*04, a strongly RA-associated allele. Finally, Thr at position 565 in the TAP2 gene was associated with manifestations of disease severity in only a few patients. Examination of TAP1 and TAP2 gene polymorphisms in RA patients revealed an association between a particular amino acid residue, namely Thr565 in the TAP2 gene, and RA. This association was found to be weak and did not seem to be a predictor for the severity of the disease.

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“…Genes encoding the two TAP subunits, TAP1 and TAP2 are located within the MHC class II region between the DPB1 and DQB1 loci [5,6], and variations in rat TAP genes have been reported to be associated with differences in the spectrum of MHC class I‐binding peptides [7]. Many diseases associated with HLA have been investigated for the influence of TAP [8–13]. Two dimorphic sites within TAP1, Ile/Val‐333 and Asp/Gly‐637, and four dimorphic sites within TAP2, Val/Ile‐379, Ala/Thr‐565, Thr/Ala‐665 and Stop/Gln‐687, have been widely investigated [9].…”

Section: Introductionmentioning

confidence: 99%

Distribution of HLA‐A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitis

Lee¹,

Ha²,

Han

et al. 2001

Clin Experimental Allergy

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Polymorphism of TAP1 and TAP2 in Japanese patients with rheumatoid arthritis

Cited by 15 publications

References 9 publications

Analysis of single‐nucleotide polymorphisms in Japanese rheumatoid arthritis patients shows additional susceptibility markers besides the classic shared epitope susceptibility sequences

Analysis of single‐nucleotide polymorphisms in Japanese rheumatoid arthritis patients shows additional susceptibility markers besides the classic shared epitope susceptibility sequences

TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France

Distribution of HLA‐A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitis

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