HLA-A*11 and novel associations in Malays and Chinese with systemic lupus erythematosus

Mohd-Yusuf, Yusmin; Phipps, Maude E.; Chow, S. K.; Yeap, Swan Sim

doi:10.1016/j.imlet.2011.05.001

Cited by 20 publications

(22 citation statements)

References 13 publications

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“…In addition, our haplotype association results further suggested SLE-risk or SLE-protective roles for classical alleles based on the effect estimates of each amino acid haplotype. The effect directions of most classical alleles, such as *01:01, *04, *07:01, *08, *09:01, *11, *13 and *14, have been consistently observed in previous Asian studies [20][21][22] . We further evaluated if the effect sizes of the amino acid haplotypes are concordant with the previously reported effect sizes for classical alleles.…”

Section: Construction Of Asian Reference Panel For Hla Imputationsupporting

confidence: 67%

“…6) as well as other Asian population studies ( Supplementary Fig. 5) 9,[20][21][22] . In addition, we note that SLE associations at several reported SLE-risk SNPs listed in the NHGRI GWAS Catalog 23 and two independent SLE-risk SNPs in the largest fine-mapping study 9 were much weaker than that at the amino acid positions during the stepwise conditional analysis.…”

Section: Discussionmentioning

confidence: 60%

“…Alternatively, this ethnic heterogeneity between the Asian and European ancestries for this single haplotype may indicate the presence of additional or unique independent effects in HLA genes and elsewhere within the MHC in the Asian or European populations. We note that the risk effect of HLA-DRB1*07:01 has been reported in another Asian study using Malay case-control subjects 22 ; however, there was no other study that examined the SLE association of *07:01 in Asian populations due to the low frequency of the *07:01 allele and small sample sizes. When the Gly11-Tyr13-Phe26 haplotype was excluded from the comparison of haplotype effects between the Asian and European data sets, the overall correlation was highly improved (r ¼ 0.82).…”

Section: Construction Of Asian Reference Panel For Hla Imputationmentioning

confidence: 55%

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The HLA-DRβ1 amino acid positions 11–13–26 explain the majority of SLE–MHC associations

et al. 2014

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Genetic association of the major histocompatibility complex (MHC) locus is well established in systemic lupus erythematosus (SLE), but the causal functional variants in this region have not yet been discovered. Here we conduct the first fine-mapping study, which thoroughly investigates the SLE-MHC associations down to the amino acid level of major HLA genes in 5,342 unrelated Korean case-control subjects, taking advantages of HLA imputation with a newly constructed Asian HLA reference panel. The most significant association is mapped to amino acid position 13 of HLA-DRb1 (P ¼ 2.48 Â 10 À 17 ) and its proxy position 11 (P ¼ 4.15 Â 10 À 17 ), followed by position 26 in a stepwise conditional analysis (P ¼ 2.42 Â 10 À 9 ).Haplotypes defined by amino acid positions 11-13-26 support the reported effects of most classical HLA-DRB1 alleles in Asian and European populations. In conclusion, our study identifies the three amino acid positions at the epitope-binding groove of HLA-DRb1 that are responsible for most of the association between SLE and MHC.

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Section: Construction Of Asian Reference Panel For Hla Imputationsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 60%

Section: Construction Of Asian Reference Panel For Hla Imputationmentioning

confidence: 55%

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The HLA-DRβ1 amino acid positions 11–13–26 explain the majority of SLE–MHC associations

et al. 2014

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“…Yusmin et al. (Mohd‐Yusuf, Phipps, Chow, & Yeap, ) has ever analyzed HLA alleles in 160 SLE patients (99 Chinese and 61 Malays) and 107 healthy control individuals (58 Chinese and 49 Malays) by sequence specific primer amplification (PCR‐SSP) phototyping techniques, and found that allele frequencies of DQB1*0301 was significantly increased in Malay and Chinese SLE patients compared with healthy control individuals. By performing analyses of HLA‐DQ alleles through conditioning on the HLA‐DRB1 alleles, David et al.…”

Section: Discussionmentioning

confidence: 99%

HLA‐DQβ1 amino acid position 87 and DQB1*0301 are associated with Chinese Han SLE

Sun

Yang

Fei

et al. 2018

Molec Gen & Gen Med

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BackgroundSeveral susceptibility loci have been identified associated with Chinese Han systemic lupus erythematosus (SLE).MethodsWe carried out imputation of classical HLA alleles, amino acids and Single Nucleotide Polymorphisms (SNPs) across the MHC region in Chinese Han SLE genome‐wide association study (GWAS) of mainland and Hong Kong populations for the first time using newly constructed Han‐MHC reference panel followed by stepwise conditional analysis.ResultsWe mapped the most significant independent association to HLA‐DQβ1 at amino acid position (Phe87, p = 7.807 × 10−17) and an independent association at HLA‐DQB1*0301 (P condiational = 1.43 × 10−7).ConclusionOur study illustrates the value of population‐specific HLA reference panel for fine‐mapping causal variants in the MHC.

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“…A recent comprehensive study conducted by Mohd-Yusuf and coworkers [19] in Malaysia revealed that HLA A∗1101, 1102, DRB5∗01-02, DQB1∗05, DRB3∗0101, 0201, 0202, 0203, 0301, and DQB1∗0301, 0304 were significantly associated with SLE in Malaysians. In addition, DRB1∗0701 and DRB4∗0101101, 0102, 0103 alleles were significantly increased in the Malay SLE patients, whilst DRB1∗1601-1606 (DR2 subtype) and DRB5∗0101, 0102, 0201, 0202, 0203 alleles were significantly higher in Chinese SLE patients.…”

Section: Candidate Genesmentioning

confidence: 99%

Genetic Risk Factors of Systemic Lupus Erythematosus in the Malaysian Population: A Minireview

Chai

Phipps

Chua

2012

Clinical and Developmental Immunology

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SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes include MHC genes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring in MHC genes and genes coding for TNF-α, IL-1β, IL-1RN, and IL-6.

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HLA-A*11 and novel associations in Malays and Chinese with systemic lupus erythematosus

Cited by 20 publications

References 13 publications

The HLA-DRβ1 amino acid positions 11–13–26 explain the majority of SLE–MHC associations

The HLA-DRβ1 amino acid positions 11–13–26 explain the majority of SLE–MHC associations

HLA‐DQβ1 amino acid position 87 and DQB1*0301 are associated with Chinese Han SLE

Genetic Risk Factors of Systemic Lupus Erythematosus in the Malaysian Population: A Minireview

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