白介素-32 基因多态性及血清水平与多发性硬化遗传易感性的关联性

目的:探讨IL-32 基因rs28372698A/ T、rs12934561C/ T 及rs11861531C/ T 三个位点的多态性与多发性硬化(MS)的遗传易感的关系,为MS 高危人群的确立提供理论依据。方法:入选580 例MS 患者和650 例健康对照,应用单碱基延伸法和DNA 测序对IL-32 基因位点进行基因分型,同时,采用酶联免疫吸附试验检测两组IL-32 的血清浓度。结果:IL-32 基因rs28372698A/ T 位点的基因型频率和对照组比较存在显著差异(P =0.007),其等位基因频率在两组间的分布频率存在统计差异(P =0.033)。rs12934561C/ T 与rs11861531C/ T 的各基因型及等位基因频率在两组间差异无统计学意义(P>0.05)。T-T-T单倍型在HCC 中的分布频率显著高于对照组(P = 0.012),T-T-T 单倍型与MS 的发病风险密切相关(OR = 1.968,95% CI:1.352-2.574)。MS 患者组的血清IL-32 水平明显高于对照组(399.08±156.85)pg/ ml vs(239.99±88.35)pg/ ml,P =0.001]。AT 和TT 基因型的MS 患者IL-32 血清水平明显高于AA 基因型MS 患者(465.53 ±172.40) pg/ mL vs (295.86 ±103.96)pg/ ml,P<0.01;(491.15±133.65)pg/ ml vs (295.86±103.96)pg/ ml,P<0.01]。结论:本研究首次报道了IL-32 基因rs28372698 位点多态性与MS 的关系,且IL-32 的基因多态性在MS 患者中对IL-32 的血清水平有影响。我们的研究为MS 遗传和个体化的诊疗提供了新的参考依据。

Association of interleukin-32 gene polymorphism and its serum levels with genetic susceptibility in patients with multiple sclerosis

Objective:To investigate interleukin-32 (IL-32)(rs28372698A/ T,rs12934561C/ T and rs11861531C/ T) genetic susceptibility in patients with multiple sclerosis(MS) by case-control study,which provides a theoretical foundation for high-risk population with MS.Methods:A total 580 MS patients and 650 healthy controls were included in this study,polymerase chain reaction-single base extension (PCR-SEB) was used to test DNA sequencing,and serum levels of IL-32 were determined by enzyme-linked immunosorbent assay.Results:The genotype and allele frequency of IL-32 (rs28372698A/ T) had significantly differences compared with healthy controls (P =0.007,P =0.033),however,there were no statistical differences in rs12934561C/ T and rs11861531C/ T between the two groups (P>0.05).T-T-T haploid genotype in patients with MS was higher than control groups (P =0.012),and T-T-T haploid genotype was associated with increased risk of MS (OR=1.968,95%CI:1.968-1.352).Serum levels of IL-32 in patients with MS was increased compared with control groups (399.08±156.85) pg/ ml vs (239.99 ±88.35) pg/ ml, P = 0.001].The serum IL-32 concentrations in MS patients with AT and TT genotype were higher compared with MS patient with AA genotype(465.53±172.40) pg/ ml vs (295.86±103.96)pg/ ml,P<0.01;(491.15±133.65)pg/ ml vs (295.86±103.96)pg/ml,P<0.01]. Conclusion:Our study found that an association between IL-32 (rs28372698) gene polymorphism and MS,and serum levels of IL-32 were influenced by IL-32 gene polymorphism in patients with MS,suggesting a theoretical basis for individualized diagnosis and treatment of MS patients.