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Objective To examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry. Methods HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B∗27-negative patients with AS were analysed separately, and logistic regression and â € relative predispositional effects' (RPE) analyses were carried out to control for the major effect of HLA-B∗27 on disease susceptibility. Results Although numerous associations were seen between HLA alleles and AS in whites, among HLA-B∗27-negative patients with AS, positive associations were seen with HLA-A∗29, B∗38, B∗49, B∗52, DRB1∗11 and DPB1∗03:01 and negative associations with HLA-B∗07, HLA-B∗57, HLA-DRB1∗15:01, HLA-DQB1∗02:01 and HLA-DQB1∗06:02. Additional associations with HLA-B∗14 and B∗40 (B60) were observed via RPE analysis, which excludes the HLA-B∗27 alleles. The increased frequency of HLA-B∗40:01 and decreased frequency of HLA-B∗07 was also seen in Han Chinese and African-Americans with AS. HLA-B∗08 was decreased in whites with acute anterior uveitis. Conclusions These data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B∗27 to be operative in AS predisposition.

ObjectiveTo examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry.MethodsHLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B*27-negative patients with AS were analysed separately, and logistic regression and 'relative predispositional effects' (RPE) analyses were carried out to control for the major effect of HLA-B*27 on disease susceptibility.ResultsAlthough numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with HLA-A*29, B*38, B*49, B*52, DRB1*11 and DPB1*03:01 and negative associations with HLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01 and HLA-DQB1*06:02. Additional associations with HLA-B*14 and B*40 (B60) were observed via RPE analysis, which excludes the HLA-B*27 alleles. The increased frequency of HLA-B*40:01 and decreased frequency of HLA-B*07 was also seen in Han Chinese and African-Americans with AS. HLA-B*08 was decreased in whites with acute anterior uveitis.ConclusionsThese data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.

Background: The HLA-B{*}58:01 allele is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) in certain geographic regions, but the diversity of the correlation is large. In addition, the currently available HLA-B{*}58:01 testing methods are too laborious for use in routine clinical detection. The objective of this study was to develop a new, convenient method for the detection of HLA-B{*}58:01 and to investigate the association of HLA-B{*}58: 01 with allopurinol-induced sCADR in a Han Chinese population. Methods: A new method combining sequence-specific primers (SSP) and TaqMan probe amplification was developed in this study and was used to detect the HLA-B{*}58:01 in 48 allopurinol-induced sCADR, 133 allopurinol-tolerant, and 280 healthy individuals. The accuracy, sensitivity, and specificity were assessed by a commercial PCR-SSP HLA-B typing kit. The low limit of detection was detected by serial dilution of an HLA-B{*}58:01-positive DNA template. Results: The new method successfully identified HLAB{*}58: 01 in thousands of HLA-B alleles, and the results for 344 DNA samples were perfectly concordant with the results of the commercial PCR-SSP HLA-B kit. The analytical sensitivity is 100% and the specificity is over 99%. The low limit of detection of this assay is 100 pg DNA, which was 10 times more sensitive than the commercial PCR-SSP kit. HLA-B{*}58:01 was present in 93.8% of the patients with sCADR, 7.5% of the allopurinol-tolerant patients, and 12.1% of the healthy controls. The frequency of HLAB{*} 58: 01 was significantly higher in the sCADR group than in the control group (p < 0.0001). However, there was no significant difference between the allopurinol-tolerant and control groups (p = 0.1547). Conclusions: HLA-B{*}58:01 has a strong association with allopurinol-induced sCADR in Han Chinese. The newly developed method is reliable for HLA-B{*}58:01 detection prior to allopurinol therapy.

Background: The HLA-B{*}58:01 allele is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) in certain geographic regions, but the diversity of the correlation is large. In addition, the currently available HLA-B{*}58:01 testing methods are too laborious for use in routine clinical detection. The objective of this study was to develop a new, convenient method for the detection of HLA-B{*}58:01 and to investigate the association of HLA-B{*}58: 01 with allopurinol-induced sCADR in a Han Chinese population. Methods: A new method combining sequence-specific primers (SSP) and TaqMan probe amplification was developed in this study and was used to detect the HLA-B{*}58:01 in 48 allopurinol-induced sCADR, 133 allopurinol-tolerant, and 280 healthy individuals. The accuracy, sensitivity, and specificity were assessed by a commercial PCR-SSP HLA-B typing kit. The low limit of detection was detected by serial dilution of an HLA-B{*}58:01-positive DNA template. Results: The new method successfully identified HLAB{*}58: 01 in thousands of HLA-B alleles, and the results for 344 DNA samples were perfectly concordant with the results of the commercial PCR-SSP HLA-B kit. The analytical sensitivity is 100% and the specificity is over 99%. The low limit of detection of this assay is 100 pg DNA, which was 10 times more sensitive than the commercial PCR-SSP kit. HLA-B{*}58:01 was present in 93.8% of the patients with sCADR, 7.5% of the allopurinol-tolerant patients, and 12.1% of the healthy controls. The frequency of HLAB{*} 58: 01 was significantly higher in the sCADR group than in the control group (p < 0.0001). However, there was no significant difference between the allopurinol-tolerant and control groups (p = 0.1547). Conclusions: HLA-B{*}58:01 has a strong association with allopurinol-induced sCADR in Han Chinese. The newly developed method is reliable for HLA-B{*}58:01 detection prior to allopurinol therapy.

Background: The HLA-B{*}58:01 allele is associated with allopurinol-induced severe cutaneous adverse drug reactions (sCADR) in certain geographic regions, but the diversity of the correlation is large. In addition, the currently available HLA-B{*}58:01 testing methods are too laborious for use in routine clinical detection. The objective of this study was to develop a new, convenient method for the detection of HLA-B{*}58:01 and to investigate the association of HLA-B{*}58: 01 with allopurinol-induced sCADR in a Han Chinese population. Methods: A new method combining sequence-specific primers (SSP) and TaqMan probe amplification was developed in this study and was used to detect the HLA-B{*}58:01 in 48 allopurinol-induced sCADR, 133 allopurinol-tolerant, and 280 healthy individuals. The accuracy, sensitivity, and specificity were assessed by a commercial PCR-SSP HLA-B typing kit. The low limit of detection was detected by serial dilution of an HLA-B{*}58:01-positive DNA template. Results: The new method successfully identified HLAB{*}58: 01 in thousands of HLA-B alleles, and the results for 344 DNA samples were perfectly concordant with the results of the commercial PCR-SSP HLA-B kit. The analytical sensitivity is 100% and the specificity is over 99%. The low limit of detection of this assay is 100 pg DNA, which was 10 times more sensitive than the commercial PCR-SSP kit. HLA-B{*}58:01 was present in 93.8% of the patients with sCADR, 7.5% of the allopurinol-tolerant patients, and 12.1% of the healthy controls. The frequency of HLAB{*} 58: 01 was significantly higher in the sCADR group than in the control group (p < 0.0001). However, there was no significant difference between the allopurinol-tolerant and control groups (p = 0.1547). Conclusions: HLA-B{*}58:01 has a strong association with allopurinol-induced sCADR in Han Chinese. The newly developed method is reliable for HLA-B{*}58:01 detection prior to allopurinol therapy.

Free to read Objective To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. Methods A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. Results Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10 -21), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10-16), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10-15). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10-18), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10-8). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. Conclusion This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants. Copyright © 2014 by the American College of Rheumatology.

Methods. Genotyping of three variants in BANK1 was carried out by unlabelled probe high resolution melting (HRM) assay in 264 SLE cases and 268 controls in a Chinese Han population living in Shanghai region. The genotype frequencies of the detected polymorphisms were analysed in relation to the production of autoantibodies (ANA, anti-dsDNA, anti-RNP, anti-SSA, anti-SSB and anti-Smith) in SLE patients. Results. Samples with the target genotypes were accurately detected and easily distinguishable by unlabelled probe HRM assay. The frequencies of the rs10516487 C allele and the rs17266594 T allele were significantly increased compared with the controls (C allele: 88.6 vs 83.2%, P = 0.011; T allele: 88.3 vs 83.2%, P = 0.019). However, the frequencies of the rs3733197 G allele were not associated with SLE (G allele: 79.9 vs 79.1%, P = 0.741). The rs10516487 and rs17266594 polymorphisms were significantly associated with high-titre ANA (epsilon 1 : 320) and production of anti-SSA antibodies in SLE patients compared with the control subjects. Conclusions. Genotyping using unlabelled probes is a rapid, accurate and cost-effective closed-tube method. This study implies that rs10516487 and rs17266594 polymorphisms might contribute to individual susceptibility to SLE and influence the ANA/SSA autoantibody response in SLE patients in Chinese population.

Methods. Genotyping of three variants in BANK1 was carried out by unlabelled probe high resolution melting (HRM) assay in 264 SLE cases and 268 controls in a Chinese Han population living in Shanghai region. The genotype frequencies of the detected polymorphisms were analysed in relation to the production of autoantibodies (ANA, anti-dsDNA, anti-RNP, anti-SSA, anti-SSB and anti-Smith) in SLE patients. Results. Samples with the target genotypes were accurately detected and easily distinguishable by unlabelled probe HRM assay. The frequencies of the rs10516487 C allele and the rs17266594 T allele were significantly increased compared with the controls (C allele: 88.6 vs 83.2%, P = 0.011; T allele: 88.3 vs 83.2%, P = 0.019). However, the frequencies of the rs3733197 G allele were not associated with SLE (G allele: 79.9 vs 79.1%, P = 0.741). The rs10516487 and rs17266594 polymorphisms were significantly associated with high-titre ANA (epsilon 1 : 320) and production of anti-SSA antibodies in SLE patients compared with the control subjects. Conclusions. Genotyping using unlabelled probes is a rapid, accurate and cost-effective closed-tube method. This study implies that rs10516487 and rs17266594 polymorphisms might contribute to individual susceptibility to SLE and influence the ANA/SSA autoantibody response in SLE patients in Chinese population.

Methods. Genotyping of three variants in BANK1 was carried out by unlabelled probe high resolution melting (HRM) assay in 264 SLE cases and 268 controls in a Chinese Han population living in Shanghai region. The genotype frequencies of the detected polymorphisms were analysed in relation to the production of autoantibodies (ANA, anti-dsDNA, anti-RNP, anti-SSA, anti-SSB and anti-Smith) in SLE patients. Results. Samples with the target genotypes were accurately detected and easily distinguishable by unlabelled probe HRM assay. The frequencies of the rs10516487 C allele and the rs17266594 T allele were significantly increased compared with the controls (C allele: 88.6 vs 83.2%, P = 0.011; T allele: 88.3 vs 83.2%, P = 0.019). However, the frequencies of the rs3733197 G allele were not associated with SLE (G allele: 79.9 vs 79.1%, P = 0.741). The rs10516487 and rs17266594 polymorphisms were significantly associated with high-titre ANA (epsilon 1 : 320) and production of anti-SSA antibodies in SLE patients compared with the control subjects. Conclusions. Genotyping using unlabelled probes is a rapid, accurate and cost-effective closed-tube method. This study implies that rs10516487 and rs17266594 polymorphisms might contribute to individual susceptibility to SLE and influence the ANA/SSA autoantibody response in SLE patients in Chinese population.