Are genetic variations in IL‐21–IL‐23R–IL‐17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta‐analysis

Mohammadi, Fatemeh; Aslani, Saeed; Mostafaei, Shayan; Jamshidi, Ahmadreza; Riahi, Parisa; Mahmoudi, Mahdi

doi:10.1002/jcp.28495

Cited by 20 publications

(15 citation statements)

References 64 publications

(48 reference statements)

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“…The 95% CrI is the Bayesian equivalent for standard confidence intervals. In particular, the model supposes that the mean of the Log ORs has a low-informative normal distribution (mean = 0, variance = 100) and the variance of the Log ORs has a low-informative inverse-gamma distribution (0.01, 0.01) [24]. Sensitivity analyses with different choices of low-information prior distributions showed the robustness of this choice [20].…”

Section: Bayesian Meta-analysis Methodsmentioning

confidence: 99%

Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis

Shao¹,

Shen²,

Zhao³

et al. 2020

J. Cancer

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XPO5/RAN-GTP complex mediates the nuclear transport of pre-miRNAs in the miRNA processing system, its altered expression is indicated to be correlated with cancer risk. Several studies have inspected the association between XPO5 or RAN polymorphisms and the risk of various cancers, but the findings remain controversial. A Bayesian hierarchical meta-analysis was carried out to review and analyze the effect of XPO5 and RAN polymorphisms on cancer risk. The association was estimated by calculating the logarithm of odds ratio (Log OR) and 95% credible interval (95% CrI). The expression quantitative trait loci (eQTL) analysis was used for in silico functional validation of the identified significant susceptibility loci. Consequently, 38 case-control studies (from 27 citations) with 27,459 cancer cases and 25,151controls were included in the meta-analysis of the five most prevalent SNPs (rs11077 A/C, rs2257082 G/A, rs3803012 A/G, rs14035 C/T, rs3809142 C/T). In the XPO5 gene rs11077 SNP, the minor C allele significantly increased the risk of cancer (Log OR = 0.120, 95% CrI = 0.013, 0.241), and a strong association between rs11077 SNP and cancer risk was also found in the dominant model (CC + AC vs. AA: Log OR = 0.132, 95% CrI = 0.009, 0.275). In addition, the minor GG genotype allele of the RAN gene rs3803012 SNP significantly increased the cancer risk (Log OR = 0.707, 95% CrI = 0.059, 1.385). Statistically significant associations between rs3803012 SNP and cancer risk were also observed in the recessive model (GG vs. AG + AA: Log OR = 0.708, 95% CrI = 0.059, 1.359). Furthermore, the eQTL analysis revealed that rs11077 SNP was significantly correlated with XPO5 mRNA expression, which provided additional biological basis for the observed positive association. Our results suggest that XPO5 rs11077 may be a possible functional susceptibility locus for cancer risk.

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Section: Bayesian Meta-analysis Methodsmentioning

confidence: 99%

Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis

Shao¹,

Shen²,

Zhao³

et al. 2020

J. Cancer

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“…The rs12722495 polymorphism of this gene correlates with its mRNA and protein expression in stimulated monocytes, naive T-cells, and memory T-cells [ 6 ]. Additionally, according to a meta-analysis of 37 studies, a minor allele A of the rs1343151 polymorphism in the IL23R gene, which encodes the receptor for interleukin 23, is associated with a risk of developing RA [ 23 ].…”

Section: Genetic Predisposition For Rheumatoid Arthritismentioning

confidence: 99%

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

Mikhaylenko

Немцова

Bure

et al. 2020

IJMS

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Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.

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“…Recently, Mohammadi et al also made Bayesian meta-analysis about polymorphisms of inflammatory cytokines and RA risk; however, positive results were found about genetic polymorphisms of IL23R gene, but not IL-21 and IL17A genes. Moreover, RF and ACPA status were not involved [44], which were the different and innovate about present study.…”

Section: Discussionmentioning

confidence: 95%

IL-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility

Hou

Zheng

et al. 2020

Bioscience Reports

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Interleukin-21 (IL-21) is a cytokine that plays a crucial role in pathogenesis and activity of the rheumatoid arthritis (RA). Meanwhile, genetic polymorphisms in the IL-21 gene may alter its expression. Previous studies have reported conflicting results assessing the association between the IL-21 rs6822844 G/T polymorphism and RA risk. Thus, it’s necessary to perform a meta-analysis to definite above relationship. PubMed database was searched for all papers published until October 20, 2019. Nine case–control studies with 9998 cases and 10742 controls were retrieved based on the search criteria at last. Odds ratio (95% confidence interval) was used to calculate the strength of this association. Publication bias was detected using both Begg’s and Egger’s tests. Overall, the IL-21 rs6822844 G/T polymorphism was found to be significantly associated with decreased RA risk (e.g. T-allele versus G-allele: OR = 0.81, 95% CI = 0.72–0.91, P < 0.001). In addition, decreased RA risk was also detected both in Asians (eg: TT+TG versus GG: OR = 0.42, 95% CI = 0.31–0.56, P < 0.001) and Caucasians (eg: TT+TG versus GG: OR = 0.85, 95% CI = 0.80–0.91, P < 0.001). A similar trend in association was found in the source of the control and genotype method subgroups. Furthermore, subgroup analysis of rheumatoid factor status revealed a protective relationship between the IL-21 rs6822844 G/T polymorphism and RF+/RF- RA risk. A similar relationship was noted in the anti-citrullinated protein antibody status subgroup. The results of the present study suggest that the IL-21 rs6822844 G/T polymorphism was significantly associated with decreased RA susceptibility.

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Are genetic variations in IL‐21–IL‐23R–IL‐17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta‐analysis

Cited by 20 publications

References 64 publications

Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis

Association of microRNA biosynthesis genes XPO5 and RAN polymorphisms with cancer susceptibility: Bayesian hierarchical meta-analysis

Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response

IL-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility

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