HLA-B*40:01 Is Associated with Ankylosing Spondylitis in HLA-B27–positive Populations

Díaz‐Peña, Roberto; Vidal-Castiñeira, José Ramón; López-Vázquez, Antonio; López‐Larrea, Carlos

doi:10.3899/jrheum.151096

Cited by 18 publications

(16 citation statements)

References 10 publications

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“…identified SNPs predicting treatment response to the first anti-TNFα agent in AS. [21][22][23] In this study, we consistently demonstrate that there are significant correlations between NLRP3 polymorphisms, NLRP3…”

Section: Discussionsupporting

confidence: 73%

The association of NLRP3 and TNFRSF1A polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept

Zhao¹,

Chen²,

Wu³

et al. 2017

Clinical Laboratory Analysis

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Section: Discussionsupporting

confidence: 73%

The association of NLRP3 and TNFRSF1A polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept

Zhao¹,

Chen²,

Wu³

et al. 2017

Clinical Laboratory Analysis

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“…with HLA-B27, such as its peptide-binding characteristics, folding rate, and whether it forms homodimers, are indicated to investigate its association further. No protective association was seen with HLA-B*07 as has previously been reported in East Asians [3] and European descent cohorts [1,15], although the allele frequency was very low and the study may not have had adequate power to detect any association with the allele (frequency = 0.024).…”

Section: Discussionmentioning

confidence: 58%

“…This study confirms that in East Asians, the primary MHC associations with AS are with HLA-B*27 and HLA-B*40, and confirms the risk association of HLA-C*1502 with the disease. The association of HLA-B*40 with AS has been convincingly demonstrated now in both European descent [1,[14][15][16] and East Asian studies [3,17], using both direct genotyping-and imputationbased methods. HLA-B*4001 has also been shown to be associated with IgA nephropathy (OR = 1.34, P = 5.64 × 10 −7 ) [18], a known though uncommon association of AS.…”

Section: Discussionmentioning

confidence: 87%

MHC associations of ankylosing spondylitis in East Asians are complex and involve non-HLA-B27 HLA contributions

Wang

Kim

et al. 2020

Arthritis Res Ther

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Background: The association of HLA-B*27 with AS is amongst the strongest of any known association of a common variant with any human disease. Nonetheless, there is strong evidence indicating that other HLA-B alleles are involved in the disease. European ethnicity studies have demonstrated risk associations with HLA-B*40 and multiple other HLA-B, HLA-A, and HLA class II alleles, and demonstrated that in that ethnic group, the amino acid sequence at position 97 in HLA-B is the key determinant of HLA associations with AS. A recent study in Korean AS cases and controls additionally identified association at HLA-C*15:02. In the current study, we examined the MHC associations of AS in an expanded East Asian cohort. Methods: A total of 1637 Chinese, Taiwanese, and Korean AS cases meeting the modified New York Criteria for AS, and 1589 ethnically matched controls, were genotyped with the Illumina Immunochip, including a dense coverage of the MHC region. HLA genotypes and amino acid composition were imputed using the SNP2HLA programme using the Han-MHC reference panel based on the data of Han Chinese subjects (n = 9689), and association tested using logistic regression controlling for population stratification effects. Results: A strong association was seen with HLA-B*27 (odds ratio (OR) = 205.3, P = 5.76 × 10 −244). Controlling for this association, the strongest risk association is seen with HLA-C*15 at genome-wide significant level (OR = 7.62, P = 9.30 × 10 −19), and confirmed association is also seen with HLA-B*40 at suggestive level (OR = 1.65, P = 2.54 × 10 −4). At amino acid level, the strongest association seen in uncontrolled analysis was with histidine at position 114 in HLA-B (P = 7.24 × 10 −241), but conditional analyses suggest that the primary amino acid associations are with lysine at position 70 and asparagine at position 97. Restriction of the ERAP1 association with HLA-B27-positive AS, previously reported in European subjects, was confirmed in East Asians.

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“…No protective association was seen with HLA-B*07 as has previously been reported in east Asians [3] and European descent cohorts [1,15], although the allele frequency was very low and the study may not have had adequate power to detect any association with the allele (frequency=0.024).…”

Section: Discussionmentioning

confidence: 57%

“…This study confirms that in East Asians the primary MHC associations with AS are with HLA-B*27 and HLA-B*40, and confirms the risk association of HLA-C*1502 with the disease. The association of HLA-B*40 with AS has been convincingly demonstrated now in both European-descent [1,[14][15][16] and east Asian studies [3,17], using both direct genotyping and imputation based methods. HLA-B*4001 has also been shown to be associated with IgA nephropathy (OR=1.34, P=5.64x10 -7 ) [18], a known though uncommon association of AS.…”

Section: Discussionmentioning

confidence: 87%

MHC associations of ankylosing spondylitis in East Asians are complex and involve non-HLA-B27 HLA contributions

Wang

Kim

et al. 2020

Preprint

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Background The association of HLA-B*27 with AS is amongst the strongest of any known association of a common variant with any human disease. Nonetheless, there is strong evidence indicating that other HLA-B alleles are involved in the disease. Large studies in European case-control cohorts have demonstrated risk associations with HLA-B*40 and multiple other HLA-B, -A and Class II alleles, and demonstrated that in that ethnic group the amino acid sequence at position 97 in HLA-B is the key determinant of HLA associations with AS. A recent study in Korean AS cases and controls additionally identified association at HLA-C*15:02. In the current study we examined the MHC associations of AS in an expanded east Asian cohort. Methods 1,637 Chinese, Taiwanese and Korean AS cases meeting the modified New York Criteria for AS, and 1,589 ethnically matched controls, were genotyped with the Illumina Immunochip, including a dense coverage of the MHC region. HLA genotypes and amino acid composition was imputed using the SNP2HLA program using the Han-MHC reference panel based on the data of Han Chinese subjects (largest Asian MHC reference available (n= 9,689)), and association tested using logistic regression using 10 principal components to control for population stratification effects. Results Strong association was seen with HLA-B*27 (odds ratio (OR) =205.3, P=5.764×10 -244 ). Controlling for this association, the strongest risk association is seen with HLA-C*15 at genome-wide significant level (OR = 7.62, P=9.30×10 -19 ), and confirmed association is also seen with HLA-B*40 at suggestive level (OR= 1.65, P= 2.54x10 -4 ). At amino acid level the strongest association seen in uncontrolled analysis was with histidine at position 114 in HLA-B (p=7.24 x10 -241 ), but conditional analyses suggest that the primary amino acid associations are with lysine at position 70 and asparagine at position 97. Restriction of the ERAP1 association with HLA-B27-positive AS, previously reported in European subjects, was confirmed in East Asians. Conclusions This study confirms in East Asians that the HLA associations of AS are multiple, including previously reported associations at HLA-B*27, -B*40, -C*15 , and –DRB1*01 , as well as novel associations with –DRB1*13 and –B*39 . The HLA-B associations are driven by the amino acids at positions 70 and 97, in the B-pocket of HLA-B.

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HLA-B*40:01 Is Associated with Ankylosing Spondylitis in HLA-B27–positive Populations

Cited by 18 publications

References 10 publications

The association of NLRP3 and TNFRSF1A polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept

The association of NLRP3 and TNFRSF1A polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept

MHC associations of ankylosing spondylitis in East Asians are complex and involve non-HLA-B27 HLA contributions

MHC associations of ankylosing spondylitis in East Asians are complex and involve non-HLA-B27 HLA contributions

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