» Articles » PMID: 37855981

Potential Role of SNP Rs2071475 in Rheumatoid Arthritis and Inflammatory Bowel Disease in the East Asian Population: a Mendelian Randomization Study

Overview
Specialty Pharmacology
Date 2023 Oct 19
PMID 37855981
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Previous observational studies have identified an association between rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, the causal relationship between RA and IBD in the East Asian population remains uncertain.

Methods: The two-sample Mendelian randomization (MR) analysis was conducted to elucidate the potential causal relationship between RA and IBD. Summary-level data from genome-wide association studies (GWAS) in the East Asian population were utilized, including RA (n = 19,190) and IBD (n = 6543), including Crohn's disease (CD, n = 5409) and ulcerative colitis (UC, n = 4853). The inverse variance weighted (IVW) method was employed as the primary analysis, supplemented by weighted median, weighted mode, simple median, MR-Egger, and MR-PRESSO analyses. Sensitivity analyses were conducted to assess the robustness of the results. Genetic data for RA (n = 22,515) were utilized to validate the findings in the East Asian population.

Results: The IVW method showed no significant association between genetically predicted RA and overall IBD in the East Asian population (OR = 1.028; 95% CI: 0.935-1.129; P = 0.567). The subgroup analysis revealed a positive association between RA and CD (OR = 1.268; 95% CI: 1.108-1.451; P < 0.001), while a negative association was observed with UC (OR = 0.839; 95% CI: 0.710-0.993; P = 0.041). These findings were supported by another set of RA data. Additionally, an SNP rs2071475 was identified to play an important role in CD and UC.

Conclusion: This study revealed a potential increased susceptibility to CD and a decreased susceptibility to UC in the East Asian population with RA. Furthermore, a key SNP rs2071475 was discovered along with its opposite effects in CD and UC. These findings provide new evidence for research on the corresponding molecular mechanisms and offer insights for clinical management of RA-associated IBD.

Citing Articles

Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions.

Bao Y, Gu L, Chen J, Wang H, Wang Z, Wang H J Transl Autoimmun. 2024; 9:100259.

PMID: 39554254 PMC: 11565429. DOI: 10.1016/j.jtauto.2024.100259.


Ulcerative colitis: molecular insights and intervention therapy.

Liang Y, Li Y, Lee C, Yu Z, Chen C, Liang C Mol Biomed. 2024; 5(1):42.

PMID: 39384730 PMC: 11464740. DOI: 10.1186/s43556-024-00207-w.


The Role of Interferon-Induced Proteins with Tetratricopeptide Repeats 1 and 2 in Sepsis-Induced Acute Liver Injury.

Liu Z, Yuan X, Huang Y, Gu Z, Xue L, Xue S Infect Drug Resist. 2024; 17:2337-2349.

PMID: 38882652 PMC: 11180434. DOI: 10.2147/IDR.S459838.


Shorter telomere length increases the risk of lymphocyte immunodeficiency: A Mendelian randomization study.

Wang B, Xiong Y, Li R, Zhang J, Zhang S Immun Inflamm Dis. 2024; 12(4):e1251.

PMID: 38607251 PMC: 11010948. DOI: 10.1002/iid3.1251.

References
1.
Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

2.
Liu J, van Sommeren S, Huang H, Ng S, Alberts R, Takahashi A . Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015; 47(9):979-986. PMC: 4881818. DOI: 10.1038/ng.3359. View

3.
Burgess S, Bowden J, Fall T, Ingelsson E, Thompson S . Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants. Epidemiology. 2016; 28(1):30-42. PMC: 5133381. DOI: 10.1097/EDE.0000000000000559. View

4.
Baumgart D, Sandborn W . Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007; 369(9573):1641-57. DOI: 10.1016/S0140-6736(07)60751-X. View

5.
Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K . Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014; 506(7488):376-81. PMC: 3944098. DOI: 10.1038/nature12873. View