Karimifar Mansour, Sereshti Nafiseh, Salehi Rasoul, Mousavi Maryam, Karimzadeh Hadi, Salehi Amirhossein, Pakzad Bahram
Division of Rheumatology, Department of Internal Medicine, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran.
Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Iran J Public Health. 2022 Aug;51(8):1866-1874. doi: 10.18502/ijph.v51i8.10273.
Recently, genome-wide association studies (GWAS) have discovered several single nucleotide polymorphisms (SNPs) and loci associated with the risk of systemic lupus erythematosus (SLE). rs6445975 (T>G; intronic variant) polymorphism in the gene is one of these loci. However, there was an inconsistency between the results of replicative studies on European and Asia ancestry. This study aimed to assess the possible association between rs6445975 polymorphism with SLE risk in the Iranian population.
Genotype and allele distribution of rs6445975 polymorphism were investigated in 110 patients with SLE and 115 healthy controls in Isfahan University of Medical Sciences, Isfahan, Iran in 2019 via real-time PCR high resolution melting method (HRM).
GG and TG genotypes, but not TT genotype, were associated with increased risk of SLE (GG vs TT; OR= 7.538; 95%CI [3.47, 17.066] and TG vs TT; OR=2.21; 95%CI [1.06, 4.72]). Inheritance analysis revealed that TG + GG was correlated with the increased risk of SLE disease in the dominant model (OR=3.928; 95%CI [2.056, 7.74]). Moreover, subjects with the G allele were more frequently affected with SLE than individuals with the T allele (OR= 3.55; 95%CI [2.37, 5.36]). The G allele in patients was correlated with serum concentration of CRP, ESR, anti-dsDNA antibody, C3, and C4 and presentation of some clinical manifestations such as kidney involvements and skin lesions (<0.05).
Our findings suggest a substantial association between rs6445975 polymorphism in the gene with susceptibility and clinical characteristics of SLE in the Iranian population.
最近，全基因组关联研究（GWAS）发现了几个与系统性红斑狼疮（SLE）风险相关的单核苷酸多态性（SNP）和基因座。该基因中的rs6445975（T>G；内含子变异）多态性就是这些基因座之一。然而，欧洲和亚洲血统人群的复制研究结果之间存在不一致。本研究旨在评估rs6445975多态性与伊朗人群SLE风险之间的可能关联。
2019年，通过实时PCR高分辨率熔解法（HRM），在伊朗伊斯法罕医科大学对110例SLE患者和115例健康对照者进行了rs6445975多态性的基因型和等位基因分布研究。
GG和TG基因型而非TT基因型与SLE风险增加相关（GG与TT相比；OR=7.538；95%CI[3.47,17.066]，TG与TT相比；OR=2.21；95%CI[1.06,4.72]）。遗传分析显示，在显性模型中，TG+GG与SLE疾病风险增加相关（OR=3.928；95%CI[2.056,7.74]）。此外，携带G等位基因的受试者比携带T等位基因的个体更易患SLE（OR=3.55；95%CI[2.37,5.36]）。患者中的G等位基因与血清CRP、ESR、抗双链DNA抗体、C3和C4浓度以及一些临床表现如肾脏受累和皮肤病变相关（<0.05）。
我们的研究结果表明，该基因中的rs6445975多态性与伊朗人群SLE的易感性和临床特征之间存在显著关联。
