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目的观察重症肌无力患者白细胞介素-2受体β亚单位(IL-2Rβ)基因rs228942、rs228941和rs743777位点多态性,探讨其与重症肌无力易感性和严重程度的关联性。方法采用SNPscanTM技术对480例重症肌无力患者和487例正常对照者IL-2Rβ基因rs228942、rs228941和rs743777位点进行基因分型,根据性别、发病年龄、抗乙酰胆碱受体(ACh R)抗体、伴与不伴胸腺瘤、发病后2年最严重临床分型和疾病最严重时Oosterhuis评分将重症肌无力患者分为不同亚组,比较重症肌无力组与对照组、重症肌无力各亚组与对照组、重症肌无力各亚组间等位基因频率,并在共显性、加性和过显性遗传模型下比较基因型频率。结果重症肌无力组IL-2Rβ基因rs228942位点T等位基因频率高于对照组(χ~2=4.692,P=0.030,OR=1.242,95%CI:1.021~1.511),基因型频率在加性遗传模型下差异有统计学意义(P=0.036,OR=1.230,95%CI:1.010~1.480)。重症肌无力组rs228942和rs228941位点组成的单倍域中GT单倍型频率高于对照组(χ~2=4.286,P=0.038),GG单倍型频率低于对照组(χ~2=5.333,P=0.021)。rs228942位点T等位基因频率在15~50岁亚组(χ~2=7.474,P=0.006,OR=1.380,95%CI:1.095~1.740)、不伴胸腺瘤亚组(χ~2=4.700,P=0.030,OR=1.261,95%CI:1.022~1.555)和发病后2年最严重全身型重症肌无力亚组(χ~2=4.715,P=0.030,OR=1.287,95%CI:1.025~1.617)均高于对照组。多因素前进法Logistic回归分析显示,发病年龄15~50岁(OR=9.026,95%CI:4.225~19.284;P=0.000)和>50岁(OR=9.956,95%CI:4.475~22.149;P=0.000)、伴胸腺瘤(OR=2.578,95%CI:1.393~4.773;P=0.003)和抗ACh R抗体阳性(OR=1.946,95%CI:1.179~3.214;P=0.009)均是发病后2年最严重临床分型的独立危险因素,而基因型不是独立危险因素。结论 IL-2Rβ基因rs228942位点可能与重症肌无力易感性相关,但未发现与其严重程度相关;亦未发现rs228941和rs743777位点多态性与重症肌无力易感性和严重程度相关。
Objective To investigate the rs228942, rs228941 and rs743777 polymorphisms of interleukin-2 receptor β subunit (IL-2Rβ) gene in patients with myasthenia gravis and explore their association with the susceptibility and severity of myasthenia gravis. Methods SNPscanTM was used to genotype the rs228942, rs228941 and rs743777 of IL-2Rβ gene in 480 patients with myasthenia gravis and 487 normal controls. According to sex, age of onset, antibody to ACh R, And without thymoma, the most serious clinical type 2 years after onset and the most severe disease Oosterhuis score will be divided into different subgroups of patients with myasthenia gravis, compared with myasthenia gravis group and control group, myasthenia gravis subgroups and controls Group, and myasthenia gravis subgroups, and genotype frequencies were compared under co-dominant, additive and overt genetic models. Results The frequency of T allele of rs228942 in IL-2Rβ gene was higher in the patients with myasthenia gravis (χ ~ 2 = 4.692, P = 0.030, OR = 1.242, 95% CI: 1.021-1.511) The difference was statistically significant under the genetic model (P = 0.036, OR = 1.230, 95% CI: 1.010 ~ 1.480). GT haplotype frequencies in haplotypes of rs228942 and rs228941 in myasthenia gravis group were higher than those in control group (χ ~ 2 = 4.286, P = 0.038). The frequency of GG haplotype was lower than that in control group (χ ~ 2 = 5.333, P = 0.021). The frequency of T allele in rs228942 locus was in the subgroup of 15-50 years old (χ ~ 2 = 7.474, P = 0.006, OR = 1.380,95% CI: 1.095-1.740) 4.700, P = 0.030, OR = 1.261, 95% CI: 1.022-1.555) and the most severe systemic myasthenia gravis subgroup 2 years after onset (χ ~ 2 = 4.715, P = 0.030, OR = 1.287, 95% CI : 1.025 ~ 1.617) were higher than the control group. Logistic regression analysis showed that the age of onset was 15 to 50 years (OR = 9.026, 95% CI: 4.225-19.284; P = 0.000) and> 50 years (OR = 9.956, 95% CI: 4.475-22.149; P = 0.000), with thymoma (OR = 2.578, 95% CI: 1.393-4.773; P = 0.003) and anti-ACh R antibody (OR = 1.946, 95% CI: 1.179-3.214; Independent 2 risk factors for the most severe clinical classification after 2 years, while genotype was not an independent risk factor. Conclusion The rs228942 locus of IL-2Rβ gene may be related to the susceptibility to myasthenia gravis without any correlation with the severity of IL-2Rβ gene. No association between rs228941 and rs743777 polymorphisms and susceptibility and severity of myasthenia gravis was found.