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

doi:10.1016/j.jfma.2021.09.010

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

J Formos Med Assoc. 2022 Jul;121(7):1283-1294. doi: 10.1016/j.jfma.2021.09.010. Epub 2021 Oct 10.

Authors

Chin-Man Wang¹, Yeong-Jian Jan Wu², Jing-Chi Lin², Li-Yu Huang², Jianming Wu³, Ji-Yih Chen⁴

Affiliations

¹ Department of Physical Medicine Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan.
² Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan.
³ Dept. of Veterinary and Biomedical Sciences, Dept. of Medicine, University of Minnesota, USA.
⁴ Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan. Electronic address: jychen31@adm.cgmh.org.tw.

PMID: 34645591
DOI: 10.1016/j.jfma.2021.09.010

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 (P_FDR = 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.

Keywords: Ankylosing spondylitis; B3GNT2; Polymorphism; Syndesmophyte.

MeSH terms

Asian People
C-Reactive Protein
Genetic Predisposition to Disease
Genome-Wide Association Study
HLA-B27 Antigen / genetics
HLA-B27 Antigen / metabolism
Humans
N-Acetylglucosaminyltransferases* / genetics
Spondylitis, Ankylosing* / genetics

Substances

HLA-B27 Antigen
C-Reactive Protein
N-Acetylglucosaminyltransferases
B3GNT2 protein, human