β2肾上腺素能受体基因多态性与伴发胸腺异常的重症肌无力的关系

Study of the association of β2-adrenergic receptor gene polymorphism with Myasthenia Gravis associated with thymus abnormality

目的 探讨β2肾上腺素能受体（β2-AR）16位、27位点基因多态性与伴发胸腺异常的重症肌无力（TMG）发生、胸腺组织类型的关系.方法 2002-2014年北京世纪坛医院神经内科病房及门诊的76例MG患者,伴发胸腺瘤24例,伴发胸腺增生40例,胸腺正常12例.应用PCR产物直接测序方法检测MG患者组（MGG）和75名性别、年龄相匹配的健康对照组（HCG）β2-AR基因多态性分布特征.结果 16位点存在A→G突变、27位点存在C→G突变,16位点Arg/Arg、Arg/Gly和Gly/Gly基因型频率在胸腺瘤MGG与HCG间（Х^2=0.460,P=0.895）、胸腺增生MGG与HCG间（Х^2=2.585,P=0.278）差异均无统计学意义.Arg和Gly等位基因频率在胸腺瘤MGG与HCG差异（Х^2 =0.137,P=0.711）,胸腺增生MGG与HCG差异均无统计学意义（Х^2 =0.300,P=0.584）.27位点Gln/Gln、Gln/Glu和Glu/Glu基因型频率及Gln、Glu等位基因频率在胸腺瘤MGG和HCG间（基因型P=0.866;等位基因Х^2=0.030,P=0.860）,胸腺增生MGG和HCG间（基因型P=0.907;等位基因Х^2=0.373,P=0.542）差异均无统计学意义.MGG胸腺瘤、胸腺增生和胸腺正常组间27位点差异有统计学意义（P=0.041）,三组间16位点差异无统计学意义（Х^2=3.374,P=0.497）.各组的基因型多态性分布均符合Hardy-Weinberg定律（P＞0.05）.结论 β2-AR基因16、27位点多态性与伴发胸腺异常的MG发病无明确相关性.β2-AR基因27位点多态性与MG患者胸腺不同组织类型相关.

Objective To investigate the association of two β2-adrenergic receptor （β2-AR） polymorphisms （Arg16Gly,Gln27Glu） with Myasthenia Gravis （MG） associated with thymus abnormality.Methods Among the 74 MG patients in analysis,24 cases were associated with thymoma,40 cases with thymic hyperplasia,12 with normal thymus.The genotypes of β2-AR in 76 MG （MGG） and 75 age and gender-matched healthy controls （HCG） were determined by polymerase chain reaction and nucleotide sequence determination.Results The frequencies of three genotypes （Arg/Arg,Arg/Gly,Gly/Gly） and alleles （Arg,Gly）in position 16 between MGG with thymoma and HCG （genotype Х^2 =0.460,P =0.895;allele Х^2 =0.137,P =0.711）,MGG with thymic hyperplasia and HCG were not statistically insignificant （genotype Х^2 =2.585,P =0.278;allele Х^2 =0.300,P =0.584）.The difference in distribution of the genotypes （Gln/Gln,Gln/Glu,Glu/Glu） and alleles （Gln,Glu） between MGG with thymoma and HCG （genotype P =0.866;allele Х^2 =0.030,P =0.860）,MGG with thymic hyperplasia and HCG （genotype P =0.907;allele Х^2 =0.373,P =0.542） were statistically insignificant.The genotypes distribution of position 27 in different thymus histology （thymoma,thymic hyperplasia,normal thymus） of MGG were significantly different （P =0.041）.The genotype frequencies in all groups were both in Hardy-Weinberg equilibrium （P 〉 0.05）.Conclusion Arg/Gly and Gln/Glu polymorphisms of β2-AR might have no relationship with the risk of MG associated with thymus abnormality.The genotypes polymorphism of position 27 may related with the different thymus histology of MG.