Jaqueline De Azevêdo Silva, Suelen Cristina de Lima, Thiago Sotero Fragoso, Catarina Addobbati Jordão Cavalcanti, Alexandre Domingues Barbosa, Maria Eduarda de Albuquerque Borborema, Thays Maria Costa de Lucena, Angela Luzia Branco Pinto Duarte, Sergio Crovella, Paula Sandrin-Garcia
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We investigated <i>VDR</i> SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR = 1.55, <i>p </i>= .01) and G/G genotype (OR = 2.69, <i>p </i>= .008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR = 0.66, <i>p </i>= .01; OR = 0.46, <i>p </i>= .01; OR = 0.44, <i>p </i>= .02, respectively). Regarding clinical features, we observed lower risk for: rs11168268 A/G genotype and nephritis (OR = 0.31, <i>p </i>= .01); rs4760648 T/T genotype and photosensitivity (OR = 0.24, <i>p </i>= .02); rs1540339 T/T genotype and antibody anti-dsDNA (OR = 0.19, <i>p </i>= .015); rs3890733 T/T genotype and serositis (OR = 0.10, <i>p </i>= .01). We identified a significant downregulation in <i>VDR</i> expression levels when compared patients and controls overall (<i>p </i>= 1.04e<sup>–7</sup>), in <i>Cdx-2</i> A/G and G/G (<i>p </i>= .008 and <i>p </i>= .014, respectively) and in patients with nephritis (<i>p </i>= .016)</p>\n \n <p>Our results suggested that <i>VDR</i> SNPs influence upon SLE susceptibility and in particular clinical features, acting on mRNA expression in SLE patients overall and the ones with nephritis.</p>\n </section>\n </div>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Differential distribution of vitamin D receptor (VDR) gene variants and its expression in systemic lupus erythematosus\",\"authors\":\"Jaqueline De Azevêdo Silva, Suelen Cristina de Lima, Thiago Sotero Fragoso, Catarina Addobbati Jordão Cavalcanti, Alexandre Domingues Barbosa, Maria Eduarda de Albuquerque Borborema, Thays Maria Costa de Lucena, Angela Luzia Branco Pinto Duarte, Sergio Crovella, Paula Sandrin-Garcia\",\"doi\":\"10.1111/iji.12576\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <p>Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder that displays an important genetic background. Vitamin D<sub>3</sub> (VD<sub>3</sub>) through its receptor (VDR) plays an important immunomodulatory role in autoimmune misbalance, being capable of modulating immune responses. Genetic alterations in <i>VDR</i> gene may contribute to an altered risk in SLE development and clinical manifestations. We investigated <i>VDR</i> SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR = 1.55, <i>p </i>= .01) and G/G genotype (OR = 2.69, <i>p </i>= .008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR = 0.66, <i>p </i>= .01; OR = 0.46, <i>p </i>= .01; OR = 0.44, <i>p </i>= .02, respectively). 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引用次数: 1
摘要
系统性红斑狼疮(SLE)是一种多因素自身免疫性疾病,具有重要的遗传背景。维生素D3 (VD3)通过其受体(VDR)在自身免疫失衡中起重要的免疫调节作用,能够调节免疫应答。VDR基因的遗传改变可能导致SLE发展和临床表现的风险改变。我们研究了128例SLE患者和138例健康对照(HC)的VDR snp(单核苷酸多态性)频率,以及29例患者和17例HC中与SLE易感性和临床特征相关的mRNA差异表达。我们观察到rs11168268 G等位基因(OR = 1.55, p = 0.01)和G/G基因型(OR = 2.69, p = 0.008)与SLE易感性增加相关。rs2248098 G等位基因、A/G和G/G基因型与SLE易感性降低相关(OR = 0.66, p = 0.01;OR = 0.46, p = 0.01;OR = 0.44, p = 0.02)。关于临床特征,我们观察到:rs11168268 A/G基因型和肾炎的风险较低(OR = 0.31, p = 0.01);rs4760648 T/T基因型与光敏性(OR = 0.24, p = 0.02);rs1540339 T/T基因型和抗体抗dsdna (OR = 0.19, p = 0.015);T/T基因型与血清炎的相关性(OR = 0.10, p = 0.01)。我们发现VDR的表达水平在患者和对照组的总体比较(p = 1.04e-7)、Cdx-2 a /G和G/G的表达水平(p = 0.008和p = 0.014)以及肾炎患者的表达水平(p = 0.016)均显著下调。我们的研究结果表明,VDR snp影响SLE的易感性,特别是临床特征,作用于SLE患者和肾炎患者的mRNA表达。
Differential distribution of vitamin D receptor (VDR) gene variants and its expression in systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder that displays an important genetic background. Vitamin D3 (VD3) through its receptor (VDR) plays an important immunomodulatory role in autoimmune misbalance, being capable of modulating immune responses. Genetic alterations in VDR gene may contribute to an altered risk in SLE development and clinical manifestations. We investigated VDR SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR = 1.55, p = .01) and G/G genotype (OR = 2.69, p = .008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR = 0.66, p = .01; OR = 0.46, p = .01; OR = 0.44, p = .02, respectively). Regarding clinical features, we observed lower risk for: rs11168268 A/G genotype and nephritis (OR = 0.31, p = .01); rs4760648 T/T genotype and photosensitivity (OR = 0.24, p = .02); rs1540339 T/T genotype and antibody anti-dsDNA (OR = 0.19, p = .015); rs3890733 T/T genotype and serositis (OR = 0.10, p = .01). We identified a significant downregulation in VDR expression levels when compared patients and controls overall (p = 1.04e–7), in Cdx-2 A/G and G/G (p = .008 and p = .014, respectively) and in patients with nephritis (p = .016)
Our results suggested that VDR SNPs influence upon SLE susceptibility and in particular clinical features, acting on mRNA expression in SLE patients overall and the ones with nephritis.
期刊介绍:
The International Journal of Immunogenetics (formerly European Journal of Immunogenetics) publishes original contributions on the genetic control of components of the immune system and their interactions in both humans and experimental animals. The term ''genetic'' is taken in its broadest sense to include studies at the evolutionary, molecular, chromosomal functional and population levels in both health and disease. Examples are:
-studies of blood groups and other surface antigens-
cell interactions and immune response-
receptors, antibodies, complement components and cytokines-
polymorphism-
evolution of the organisation, control and function of immune system components-
anthropology and disease associations-
the genetics of immune-related disease: allergy, autoimmunity, immunodeficiency and other immune pathologies-
All papers are seen by at least two independent referees and only papers of the highest quality are accepted.