El-Sayed Eman Hassan, Fathy Amal, Al-Deen Younes Soha Ezz, Al-Shahaly Mohsen Hassan, Omar Hanan Hassan
Clinical Pathology Department, Faculty of Medicine, Suez Canal University, 4.5 km Ring Road, P.O: 41111, Ismailia, Egypt.
Rheumatology, Physical Medicine and Rehabilitation Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Biochem Genet. 2023 Dec;61(6):2443-2456. doi: 10.1007/s10528-023-10383-z. Epub 2023 Apr 27.
Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory, autoimmune disease that could be disabling throughout its course. It affects people in their most reproductive years with relatively high morbidity and mortality. Long non-coding RNAs became one of the epigenetic mechanisms to prove a link to RA pathogenesis and development, including H19 and MALAT1 genes. These two genes' expressions had proved to increase in multiple diseases, attracting attention to their polymorphisms and their possible risk role. Assess the association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA and its disease activity. In this pilot study, 200 hundred subjects (100 RA patients and 100 healthy controls) were investigated for a possible link between the polymorphisms H19 SNP (rs2251375) and MALAT1 SNP (3200401) and RA susceptibility and disease activity. RA-related investigations and clinical assessment were done. Real-time PCR genotyping of both SNPs was done using TaqMan® MGB probes. There was no association between the SNPs and risk of developing RA. However, both SNPs had a significant association with high disease activity. H19 SNP (rs2251375) heterozygous genotype CA had an association with elevated levels of ESR (p = 0.04) and higher DAS28-ESR score (p = 0.03). MALAT1 (rs3200401) C allele had an association with elevated ESR (p = 0.001), DAS28-ESR (p = 0.03), and DAS28-CRP (p = 0.007), while CC genotype had an association with DAS28-CRP (p = 0.015). Linkage disequilibrium and haplotyping of the alleles of both SNPs were analyzed as both genes are present on chromosome 11, but no significant association was found between any of the combinations of the alleles (p > 0.05), denoting that (rs2251375) and (rs3200401) are not in linkage disequilibrium. There is no association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA. However, there is an association between H19 SNP (rs2251375) genotype CA and MALAT1 SNP (rs3200401) genotype CC with RA high disease activity.
类风湿关节炎（RA）是一种慢性、进行性、炎症性自身免疫性疾病，在其整个病程中都可能导致残疾。它在人们的生育高峰期影响人群，发病率和死亡率相对较高。长链非编码RNA成为证明与RA发病机制和发展相关的表观遗传机制之一，包括H19和MALAT1基因。这两个基因的表达已被证明在多种疾病中增加，引起了对其多态性及其可能的风险作用的关注。评估H19单核苷酸多态性（SNP，rs2251375）和MALAT1 SNP（rs3200401）与RA易感性及其疾病活动之间的关联。在这项初步研究中，对200名受试者（100名RA患者和100名健康对照）进行了调查，以研究H19 SNP（rs2251375）和MALAT1 SNP（3200401）多态性与RA易感性和疾病活动之间的可能联系。进行了与RA相关的调查和临床评估。使用TaqMan® MGB探针进行了两个SNP的实时PCR基因分型。这些SNP与患RA的风险之间没有关联。然而，这两个SNP均与高疾病活动度有显著关联。H19 SNP（rs2251375）杂合基因型CA与ESR水平升高（p = 0.04）和较高的DAS28-ESR评分（p = 0.03）相关。MALAT1（rs3200401）C等位基因与ESR升高（p = 0.001）、DAS28-ESR（p = 0.03）和DAS28-CRP（p = 0.007）相关，而CC基因型与DAS28-CRP（p = 0.015）相关。由于这两个基因都位于11号染色体上，因此对两个SNP的等位基因进行了连锁不平衡和单倍型分析，但在任何等位基因组合之间均未发现显著关联（p>0.05），这表明（rs2251375）和（rs3200401）不存在连锁不平衡。H19 SNP（rs2251375）和MALAT1 SNP（rs3200401）与RA易感性之间没有关联。然而，H19 SNP（rs2251375）基因型CA和MALAT1 SNP（rs3200401）基因型CC与RA高疾病活动度相关。
