Genetics of Ankylosing Spondylitis—Focusing on the Ethnic Difference Between East Asia and Europe

Abstract

Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis affecting the mainly axial joints in both East Asia and Europe. To date, the pathogenesis of AS is still unknown, although we know that genetics play a vital role in it. The HLA-B27 allele is found in over 85% of AS patients. However, strong evidence suggests that other major histocompatibility complex (MHC) and non-MHC genes are also involved in the pathogenesis. In addition, current data showed that there were significant differences in both genomics and metagenomics among the different ethnic populations. The investigation of the key role of the microbiome in AS pathogenesis also highlighted the host–microbiome genetic interactions. Here, we systematically review current AS genetic research data and further compare genetic differences, especially between East Asian and European groups, which may highlight the challenge in future genetic studies.

PGG.MHC: toward understanding the diversity of major histocompatibility complexes in human populations

“…In the global population prevalence map, we can see a pattern of allele frequency distribution, in which the allele is more common in Caucasian populations like European and American populations but less common in Japanese and African populations. This pattern fits the observations of previous genetic studies of AS ( 8 ), suggesting that the population prevalence visualization has potential value for genetic diversity studies of diseases.…”

“…The diversity of HLA alleles can explain the genetic difference in some diseases among populations. For example, previous studies have shown that the HLA-B*27 carrier rate correlates with the population prevalence of ankylosing spondylitis, a type of arthritis of the human spine ( 8 ). Moreover, the disease-associated HLA alleles can vary among populations of different ancestry; for instance, pemphigus vulgaris is associated with HLA-DRB1*04:02 in Ashkenazi Jews, while in non-Jewish patients with European or Asian ethnic origins, the disease is associated with HLA-DRB1*14:01/04 and HLA-DQB1*05:03 ( 9 ).…”

Population Genetics and Signatures of Selection in Early Neolithic European Farmers

“…Based on the analysis, we report the highest allele frequencies for HLA-A to be A*24:02 (0.44) and A*02:01 (0.38), B*51:01 (0.31) and B*27:05 (0.25) for HLA-B , and C*02:02 (0.25) and C*15:02 (0.23) for HLA-C ( supplementary tables S4 and S5, Supplementary Material online). In comparison, Late Neolithic individuals from the Wartberg culture show similar distributions of the HLA class I alleles, with HLA-B*27:05 at a frequency of 23% and HLA-C*02:02 at 17% ( Immel et al 2019 ), which is higher than the modern frequencies of the two alleles in Europeans being 3.73% ( Wu et al 2021 ) and 5.6% (UK pop 3 from ( Gonzalez-Galarza et al 2021 )), respectively. Interestingly, the two highest frequency HLA-B alleles in our sample, HLA-B*51:01 and HLA-B*27:05, have been associated with Behçet’s disease susceptibility ( Verity et al 1999 ; Kirino et al 2013 ) and ankylosing spondylitis (AS) ( Cauli et al 2013 ; International Genetics of Ankylosing Spondylitis Consortium (IGAS) 2013 ; Chen et al 2017 ).…”

West meets East in genetics of ankylosing spondylitis

“…It is reported that the gut microbiome of AS patients was notably different from that of healthy controls 3,4 . This discussion will primarily focus on the existing available genetic data and will make genetic comparisons between East Asian and Caucasian populations regarding AS 5 …”