AlFadhli Suad, Al-Mutairi Mashael, Al Tameemi Bader, Nizam Rasheeba
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, PO Box 31470, Sulaibekhat, Kuwait.
Clin Rheumatol. 2016 Mar;35(3):623-9. doi: 10.1007/s10067-016-3179-z. Epub 2016 Jan 27.
The expression of interferon inducible genes are reported to be heightened in systemic lupus erythematosus (SLE); nevertheless, not much is known regarding the genetic variants underlying these genes and their role in the pathogenesis of disease. Herein, we aim to explore the potential association and contribution of polymorphisms in MX1 gene (i) promoter with part of exon 1 (ii) intron 6, and (iii) their resulting haplotypes, with susceptibility to SLE. A total of 306 subjects, 152 SLE and 154 healthy controls (HC), were screened by direct sequencing method. Statistical analysis was carried out using appropriate software. The screening region of interest in MX1 revealed the existence of promoter (-123C/A, -88G/T, -20 A/C) and intron 6 (+9862G/A, +10190G/A, +9901C/G, +9920C/A, +9959C/T, +10047A/G) variants in SLE and HC. A significant association was observed between MX1 -88G/T SNP and susceptibility to SLE (χ (2) = 4.18, p = 0.04, OR = 1.89, 95 % CI 1.03-3.5). Haplotype analysis also revealed increased risk of SLE among individuals carrying CTA haplotype (-123 C, -88 T, -20 A) (χ (2) = 5.74, p = 0.017, OR = 4.28, 95 % CI 1.30-14.06). None of the other tested variants showed any significant association with SLE. The present study is the first to reveal the influence of genetic variation in MX1 gene in susceptibility to SLE.
据报道，系统性红斑狼疮（SLE）中干扰素诱导基因的表达会增强；然而，关于这些基因潜在的遗传变异及其在疾病发病机制中的作用，我们知之甚少。在此，我们旨在探究MX1基因（i）启动子与第1外显子部分、（ii）第6内含子以及（iii）它们形成的单倍型中的多态性与SLE易感性之间的潜在关联和作用。通过直接测序法对总共306名受试者进行了筛查，其中152名SLE患者和154名健康对照（HC）。使用合适的软件进行了统计分析。MX1基因的目标筛查区域显示，SLE患者和健康对照中均存在启动子（-123C/A、-88G/T、-20A/C）和第6内含子（+9862G/A、+10190G/A、+9901C/G、+9920C/A、+9959C/T、+10047A/G）变异。观察到MX1基因-88G/T单核苷酸多态性（SNP）与SLE易感性之间存在显著关联（χ² = 4.18，p = 0.04，OR = 1.89，95%可信区间1.03 - 3.5）。单倍型分析还显示，携带CTA单倍型（-123C、-88T、-20A）的个体患SLE的风险增加（χ² = 5.74，p = 0.017，OR = 4.28，95%可信区间1.30 - 14.06）。其他测试的变异均未显示与SLE有任何显著关联。本研究首次揭示了MX基因遗传变异对SLE易感性的影响。
