Evidence map›Paper›PMID 41029746›Full record

ArticleBMC medical genomics2025

Impact of interaction between IL-21 gene variants and smoking status on susceptibility to rheumatoid arthritis.

Xiang Lu, Yuan Xue, Shanle Yan

Abstract read
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Article in BMC medical genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Xiang LuDepartment of Rheumatology and Immunology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), No.9 Chongwen Road, Industrial Park, Suzhou, 215123, Jiangsu Province, China. lux_js@163.com.
Yuan XueDepartment of Rheumatology and Immunology, Shanxi Yuncheng Central Hospital, Yuncheng, 044099, Shanxi Province, China.
Shanle YanDepartment of Rheumatology and Immunology, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), No.9 Chongwen Road, Industrial Park, Suzhou, 215123, Jiangsu Province, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn recent years, interleukin-21 (IL-21) has been found to be a key player in RA pathogenesis and progression, despite accumulating evidence on rheumatoid arthritis (RA) etiology, the precise contribution of IL-21 gene variants interacting with environmental exposures remains unexplored in population-based studies. Therefore, we performed this study to evaluate the impact of gene single nucleotide polymorphisms (SNPs) and their interaction with environment on RA risk.

methodsIn this study, Genomic DNA was extracted from whole blood samples (Invitrogen PureLink™ Genomic DNA Mini Kit), and targeted genotyping of four SNPs (rs2055979, rs12508721, rs2221903 and rs907715) of IL-21 gene was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Genotypic relationship testing in this case-control study was performed by using SNPStats online software ( https://www.snpstats.net/ ), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The interaction combinations among four SNPs and environmental factors including smoking and alcohol drinking were screened using generalized multifactor dimensionality reduction (GMDR).

resultsLogistic regression analysis showed that the risks of RA were significantly higher in carriers with rs2055979- CA genotype (OR = 1.63, 95% CI = 1.28-1.97), rs2055979-AA genotype (OR = 2.02, 95% CI = 1.47-2.59), rs2055979-AA + CA genotype (OR = 1.78, 95% CI = 1.32-2.26), compared to carriers with rs2055979-CC genotype. In allele genetic model, rs2055979-A was also associated with increased RA risk (OR = 1.72, 95% CI = 1.39-2.06). However, we did not find any significant association of rs2221903, rs907715 and rs12508721 with RA risk. The GMDR model found a statistically significant two locus model (P = 0.018), including rs2055979 and smoking, indicating that the interaction between rs2055979 and smoking was significantly associated with the risk of RA. Smokers with rs2055979-AA or CA genotype had the highest risk of RA, compared with non-smokers with rs2055979-CC genotype, OR (95% CI) was 3.23 (1.86-4.64).

conclusionsWe found that rs2055979- A allele, gene- environment interaction between rs2055979 and smoking were all correlated with increased RA risk.

Indexed as

Arthritis, RheumatoidGenetic Predisposition to DiseaseInterleukinsPolymorphism, Single NucleotideSmokingAdultAgedCase-Control StudiesFemaleGene-Environment InteractionGenotypeHumansInterleukin-21MaleMiddle AgedInterleukin-21InterleukinsInteractionInterleukin-21Rheumatoid arthritisSingle nucleotide polymorphismsSmoking

Identifiers

PMID41029746
PMCPMC12482331

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