Genetic effects of B3GNT2 on ankylosing spondylitis susceptibility and clinical manifestations in Taiwanese

Chin Man Wang, Yeong Jian Jan Wu, Jing Chi Lin, Li Yu Huang, Jianming Wu, Ji Yih Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Purpose: The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods: Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results: The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion: Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

Original languageEnglish (US)
JournalJournal of the Formosan Medical Association
DOIs
StateAccepted/In press - 2021

Bibliographical note

Funding Information:
We greatly appreciate the Shin Chu Blood Donor Center for collection of samples, Dr. Su-Wei Chang for statistics analysis and Miss Chang Wei-Ling for technical help. This study was supported by funding from the Chang Gung Memorial Hospital ( CMRPG 5H0022 , CMRPG 5I0061 , CMRPG 3C0063 , CMRPG 3J1422 and CMRPG 3F0053 ) and the Ministry of Science and Technology, Taiwan ( MOST 107-2314-B-182-059-MY3 ).

Funding Information:
We greatly appreciate the Shin Chu Blood Donor Center for collection of samples, Dr. Su-Wei Chang for statistics analysis and Miss Chang Wei-Ling for technical help. This study was supported by funding from the Chang Gung Memorial Hospital (CMRPG 5H0022, CMRPG 5I0061, CMRPG 3C0063, CMRPG 3J1422 and CMRPG 3F0053) and the Ministry of Science and Technology, Taiwan (MOST 107-2314-B-182-059-MY3).

Publisher Copyright:
© 2021 Formosan Medical Association

Keywords

  • Ankylosing spondylitis
  • B3GNT2
  • Polymorphism
  • Syndesmophyte

PubMed: MeSH publication types

  • Journal Article

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