HLA-DRB1, IRF5, and CD28 gene polymorphisms in Egyptian patients with rheumatoid arthritis: susceptibility and disease activity

Said, Noha Mohamed; Ezzeldin, Nillie; Said, Dina; Ebaid, Amany; Atef, Dina M.; Atef, Rehab M.

doi:10.1038/s41435-021-00134-8

Cited by 4 publications

(2 citation statements)

References 21 publications

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“…Different genetic factors are identi ed to be associated with RA. Among different genetic factors, HLA DRB1 alleles are investigated in several studies and found to be signi cantly associated with RA [24,25]. This association has been identi ed in different populations across the world.…”

Section: Introductionmentioning

confidence: 99%

Genetic risk assessment of HLA DRB1 alleles (01, 04, 12 and 15) with Rheumatoid arthritis susceptibility among the Pashtun population of Khyber Pakhtunkhwa, Pakistan

Ilahi,

Khan,

Khan

et al. 2024

Preprint

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Background: Rheumatoid arthritis (RA) is a chronic autoimmune condition influenced by a complex interplay of genetic and environmental factors. Specific genetic variations, particularly in the human leukocyte antigen (HLA)-DRB1 gene, have been strongly linked to RA susceptibility. HLA-DRB1 alleles, part of the major histocompatibility complex (MHC) class II gene family, play a significant role in the immune system. Aims: This study aimed to investigate the association between HLA-DRB1*01, *04, *12, and *15 alleles and RA risk within the Pashtun population of Pakistan. Methods: A cohort of 100 RA patients and 80 healthy controls was recruited for this study. DNA was isolated from blood samples using the salting-out method, followed by genotyping using sequence-specific primer polymerase chain reaction (SSP-PCR). The association of the selected alleles with clinicopathological and demographic parameters of RA was assessed using the Medcalc odds ratio calculator and Chi-square test. Results: Allelic and genotypic analysis revealed that HLA-DRB1 *01 and *04 variants exhibited non-significant associations with RA risk (P=0.1421 and 0.8495, respectively). Similarly, mutant genotypes of HLA-DRB1 *01 and *04 showed non-significant associations with RA (P=0.2922 and P=0.8263, respectively). However, the heterozygous CA genotype of HLA-DRB1 *01 demonstrated a significant association with RA (P=0.0004), whereas HLA-DRB1 *04 did not (P=0.9120). Furthermore, HLA-DRB1 *12 showed a significant association with increased RA risk (P=0.0001), while HLA-DRB1 *15 did not (P=0.5519). Additionally, HLA-DRB1*01, *04, and *12 did not show significant associations with age group (P=0.08, P=0.11, P=0.16) and rheumatoid factor (RF) status (P=0.34, P=0.65, and P=0.74), whereas HLA-DRB1 *15 exhibited non-significant associations with age group and RF (P=0.01 each). Moreover, associations of HLA-DRB1 *01, *04, *12, and *15 with gender (P=0.81, P=0.52, P=0.27, and P=0.09, respectively) and anti-citrullinated protein antibody (ACPA) status (P=0.56, P=0.40, P=0.65, and P=0.008, respectively) were not significant, except for HLA-DRB1 *04, which displayed a significant association with ACPA. Conclusion: HLA-DRB1 *12 and heterozygous genotypes of HLA-DRB1 *01 were significantly associated with RA risk in the Pashtun population. However, further analysis utilizing whole exome sequencing with larger datasets is warranted for more precise results.

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Section: Introductionmentioning

confidence: 99%

Genetic risk assessment of HLA DRB1 alleles (01, 04, 12 and 15) with Rheumatoid arthritis susceptibility among the Pashtun population of Khyber Pakhtunkhwa, Pakistan

Ilahi,

Khan,

Khan

et al. 2024

Preprint

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“…TNF-like ligand 1A(TL1A), a common genetic risk locus between IBD and RA, competitively binds to death receptor 3(DR3) or decoy receptor 3(DcR3), stimulates downstream signaling pathways, and affects the regulation of effector cell proliferation, activation, and apoptosis and the production of cytokines and chemokines, which eventually affect IBD and RA progression (16,17). Additionally, polymorphisms in the interferon regulatory factor 5(IRF5) and TNF receptor superfamily member 14(TNFRSF14) motifs can predispose the susceptibility of IBD and RA (18)(19)(20)(21). Presently, detailed studies on mining shared genetic risk loci between IBD and RA are lacking; therefore, herein, we focused on identifying risk loci for these comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory bowel disease and rheumatoid arthritis share a common genetic structure

Cao,

Luo,

et al. 2024

Front. Immunol.

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BackgroundThe comorbidity rate of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) is high; nevertheless, the reasons behind this high rate remain unclear. Their similar genetic makeup probably contributes to this comorbidity.MethodsBased on data obtained from the genome-wide association study of IBD and RA, we first assessed an overall genetic association by performing the linkage disequilibrium score regression (LDSC) analysis. Further, a local correlation analysis was performed by estimating the heritability in summary statistics. Next, the causality between the two diseases was analyzed by two-sample Mendelian randomization (MR). A genetic overlap was analyzed by the conditional/conjoint false discovery rate (cond/conjFDR) method.LDSC with specific expression of gene analysis was performed to identify related tissues between the two diseases. Finally, GWAS multi-trait analysis (MTAG) was also carried out.ResultsIBD and RA are correlated at the genomic level, both overall and locally. The MR results suggested that IBD induced RA. We identified 20 shared loci between IBD and RA on the basis of a conjFDR of <0.01. Additionally, we identified two tissues, namely spleen and small intestine terminal ileum, which were commonly associated with both IBD and RA.ConclusionHerein, we proved the presence of a polygenic overlap between the genetic makeup of IBD and RA and provided new insights into the genetic architecture and mechanisms underlying the high comorbidity between these two diseases.

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The Genes Associated with Rheumatoid Arthritis Patients with Blood-Stasis Syndrome

Han,

Zhang,

Guo

et al. 2023

2023 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)

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HLA-DRB1, IRF5, and CD28 gene polymorphisms in Egyptian patients with rheumatoid arthritis: susceptibility and disease activity

Cited by 4 publications

References 21 publications

Genetic risk assessment of HLA DRB1 alleles (01, 04, 12 and 15) with Rheumatoid arthritis susceptibility among the Pashtun population of Khyber Pakhtunkhwa, Pakistan

Genetic risk assessment of HLA DRB1 alleles (01, 04, 12 and 15) with Rheumatoid arthritis susceptibility among the Pashtun population of Khyber Pakhtunkhwa, Pakistan

Inflammatory bowel disease and rheumatoid arthritis share a common genetic structure

The Genes Associated with Rheumatoid Arthritis Patients with Blood-Stasis Syndrome

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