Genome-wide association study reveals ethnicity-specific SNPs associated with ankylosing spondylitis in the Taiwanese population.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease affecting mainly spine and sacroiliac joints and adjacent soft tissues. Genome-wide association studies (GWASs) are used to evaluate genetic associations and to predict genetic risk factors that determine the biological basis of disease susceptibility. We aimed to explore the race-specific SNP susceptibility of AS in Taiwanese individuals and to investigate the association between HLA-B27 and AS susceptibility SNPs in Taiwan. METHODS: Genotyping data were collected from a medical center participating in the Taiwan Precision Medicine Initiative (TPMI) in the northern district of Taiwan. We designed a case-control study to identify AS susceptibility SNPs through GWAS. We searched the genome browser to find the corresponding susceptibility genes and used the GTEx database to confirm the regulation of gene expression. A polygenic risk score approach was also applied to evaluate the genetic variants in the prediction of developing AS. RESULTS: The results showed that the SNPs located on the sixth chromosome were related to higher susceptibility in the AS group. There was no overlap between our results and the susceptibility SNPs found in other races. The 12 tag SNPs located in the MHC region that were found through the linkage disequilibrium method had higher gene expression. Furthermore, Taiwanese people with HLA-B27 positivity had a higher proportion of minor alleles. This might be the reason that the AS prevalence is higher in Taiwan than in other countries. We developed AS polygenic risk score models with six different methods in which those with the top 10% polygenic risk had a fivefold increased risk of developing AS compared to the remaining group with low risk. CONCLUSION: A total of 147 SNPs in the Taiwanese population were found to be statistically significantly associated with AS on the sixth pair of chromosomes and did not overlap with previously published sites in the GWAS Catalog. Whether those genes mapped by AS-associated SNPs are involved in AS and what the pathogenic mechanism of the mapped genes is remain to be further studied.

Functional implications of rs9373441 with FOXP3+Treg and Tr1 for the clinical effectiveness of csDMARDs in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by a deficiency in regulatory T cells (Treg), which play a crucial role in immune regulation. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are widely used, there remains a challenge as efficacy varies among patients. In this genome-wide association study (GWAS) involving 410 RA patients, rs9373441 emerged as the most significantly linked single-nucleotide polymorphism (SNP) to csDMARDs response. This non-coding variant functions as a cis-acting regulatory element within the UTRN gene, which is associated with cortical erosion and osteoporosis. Particularly, individuals with the TT allele at rs9373441 exhibited a more favorable response, characterized by a significant increase in FOXP3 + Treg and Type 1 regulatory T cells (Tr1) (p = 0.04, 0.02) and a decrease in Effector T helper cells (Effector Th) (p = 0.03). The GATA3-GCM2-PTH and GATA3-FOXO1-FOXP3 pathways were implicated. RNA-sequencing (RNA-seq) analysis revealed increased expression levels of UTRN, PTH2R, FOXO1, and FOXO3 in good and moderate responders (p = 0.01, 0.03, 0.0005, and 0.02). Notably, the change in FOXP3 + Treg and Tr1 was positively correlated with UTRN expression (both p = 0.03). These findings underscore the critical link between rs9373441 and the response to csDMARDs, empowering clinicians to tailor treatments for enhanced outcomes in patients with RA.

Crystal-engineering and luminescence studies of 1,3,5-tris(3-pyridylethynyl)benzene or 1,3,5-tris(4-pyridylethynyl)benzene with copper(i) iodides.

Two isomeric C3-symmetric ligands, 1,3,5-tris(3-pyridylethynyl)benzene (L1) and 1,3,5-tris(4-pyridylethynyl)benzene (L2), were used to react with CuI to give a series of coordination frameworks containing various CuI clusters, {[(Cu2I2)2(L1)2]·C6H5CH3}n (1), {[(Cu2I2)1.5(L1)2]·1.5C6H6·CH3CN}n (2), [(Cu2I2)0.5(L1)]n (3), {[(Cu2I2)0.5(L2)]·C6H6}n (4), and {[(Cu2I2)(L2)]·C6H6}n (5), which have been isolated and structurally characterized by X-ray diffraction studies. Although 1 is simultaneously composed of a rhombohedral Cu2I2 cluster and a step-cubane Cu4I4 cluster and 2 contains two types of rhombohedral Cu2I2 clusters in the frameworks, both give similar 3-D supramolecular architectures interpenetrated by 2-D layer frameworks. 3 forms a 1-D double-zigzag framework, and significantly the interlocking of the 1-D frameworks into the 28-membered rings of the adjacent chains generates a novel 1-D (1-D → 1-D) polyrotaxane framework. However, as the structural and isomeric analogue, 4 only forms a 1-D double-zigzag framework leading to a 2-D supramolecular structure by ππ interactions and C-HN hydrogen bonding. 5, composed of polymeric (Cu2I2)n cluster chains, forms a 3-D coordination framework and interpenetrates to give a 2-fold interpenetrated framework. It is noted that these coordination frameworks show various structural motifs depending on the reaction conditions and ligands' backbones. In addition, the low-energy emissions at 538-615 nm for 1-5 either at room temperature or at 77 K have been observed, which are most likely to originate from an iodo-to-copper charge-transfer transition, possibly modified by Cu(i)Cu(i) interactions.