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MIR27A(rs11671784)变体与系统性红斑狼疮的关联分析

Analysis of MIR27A (rs11671784) Variant Association with Systemic Lupus Erythematous.

作者信息

Khired Zenat Ahmed, Kattan Shahad W, Alzahrani Ahmad Khuzaim, Milebary Ahmad J, Hussein Mohammad H, Qusti Safaa Y, Alshammari Eida M, Toraih Eman A, Fawzy Manal S

机构信息

Department of Surgery, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia.

Department of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu 46423, Saudi Arabia.

出版信息

Life (Basel). 2023 Mar 5;13(3):701. doi: 10.3390/life13030701.

Abstract

Multiple microRNAs (miRs) are associated with systemic autoimmune disease susceptibility/phenotype, including systemic lupus erythematosus (SLE). With this work, we aimed to unravel the association of the miR-27a gene (MIR27A) rs11671784G/A variant with SLE risk/severity. One-hundred sixty-three adult patients with SLE and matched controls were included. A TaqMan allelic discrimination assay was applied for MIR27A genotyping. Logistic regression models were run to test the association with SLE susceptibility/risk. Genotyping of 326 participants revealed that the heterozygote form was the most common genotype among the study cohort, accounting for 72% of the population (n = 234), while A/A and G/G represented 15% (n = 49) and 13% (n = 43), respectively. Similarly, the most prevalent genotype among cases was the A/G genotype, which was present in approximately 93.3% of cases (n = 152). In contrast, only eight and three patients had A/A and G/G genotypes, respectively. The MIR27A rs11671784 variant conferred protection against the development of SLE in several genetic models, including heterozygous (G/A vs. A/A; OR = 0.10, 95% CI = 0.05-0.23), dominant (G/A + G/G vs. AA; OR = 0.15, 95% CI = 0.07-0.34), and overdominant (G/A vs. A/A + G/G; OR = 0.07, 95% CI = 0.04-0.14) models. However, the G/G genotype was associated with increased SLE risk in the recessive model (G/G vs. A/A+ G/G; OR = 17.34, 95% CI = 5.24-57.38). Furthermore, the variant showed significant associations with musculoskeletal and mucocutaneous manifestations in the patient cohort ( = 0.035 and 0.009, respectively) and platelet and white blood cell counts ( = 0.034 and 0.049, respectively). In conclusion, the MIR27A rs11671784 variant showed a potentially significant association with SLE susceptibility/risk in the studied population. Larger-scale studies on multiethnic populations are recommended to verify the results.

摘要

多种微小RNA(miR)与包括系统性红斑狼疮(SLE)在内的系统性自身免疫性疾病易感性/表型相关。通过这项研究,我们旨在揭示miR - 27a基因(MIR27A)rs11671784G/A变异与SLE风险/严重程度之间的关联。纳入了163例成年SLE患者及匹配的对照。采用TaqMan等位基因鉴别分析对MIR27A进行基因分型。运用逻辑回归模型来检验与SLE易感性/风险的关联。对326名参与者的基因分型显示,杂合子形式是研究队列中最常见的基因型,占人群的72%(n = 234),而A/A和G/G分别占15%(n = 49)和13%(n = 43)。同样,病例中最常见的基因型是A/G基因型,约93.3%的病例(n = 152)为该基因型。相比之下,分别只有8例和3例患者具有A/A和G/G基因型。在包括杂合子(G/A vs. A/A;OR = 0.10,95% CI = 0.05 - 0.23)、显性(G/A + G/G vs. AA;OR = 0.15,95% CI = 0.07 - 0.34)和超显性(G/A vs. A/A + G/G;OR = 0.07,95% CI = 0.04 - 0.14)模型在内的多种遗传模型中,MIR27A rs11671784变异对SLE的发生具有保护作用。然而,在隐性模型中(G/G vs. A/A + G/G;OR = 17.34,95% CI = 5.24 - 57.38),G/G基因型与SLE风险增加相关。此外,该变异在患者队列中与肌肉骨骼和皮肤黏膜表现(分别为 = 0.035和0.009)以及血小板和白细胞计数(分别为 = 0.034和0.049)存在显著关联。总之,在研究人群中,MIR27A rs11671784变异与SLE易感性/风险显示出潜在的显著关联。建议开展更大规模的多民族人群研究以验证结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee8/10058767/5ae97013dbd1/life-13-00701-g001.jpg

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