肿瘤坏死因子-α基因多态性与安徽地区汉族人群Graves病易感性及患病早期TRAb水平的关联

Association of TNF-a gene polymorphisms with Graves disease susceptibility and early course thyroid stimulating hormone receptor antibody level in Chinese Han population in Anhui region

目的检测肿瘤坏死因子-α（tumournecrosisfactor-α，TNF—α）基因启动子区的-863C／A、-857C／T、-238G／A等3个位点的单核苷酸多态性与格雷夫斯氏病（Gravesdisease，GD）与安徽地区汉族人群中发病的相关性，以探讨与GD有关的遗传背景。方法应用聚合酶链式反应-序列特异性引物法（polymerasechainreactionandsequencespecificprimers，PCR-SSP）检测254例Graves病患者和212名正常对照 TNF-α基因启动子区-863C／A、-857C／T、-238G／A三个位点的单核苷酸多态性，比较GD患者组与正常对照组、不同性别的GD患者之间的等位基因和基因型频率的分布情况。同时采用放射性免疫法测定早期GD患者的促甲状腺激素受体抗体（thyroidstimulatinghormonereceptorantibody，TRAb）水平，比较不同TRAb水平患者TNFma基因这3个多态位点等位基因及基因型的频率分布情况。结果（1）GD组-863C／A位点A等位基因频率（16．73％）高于正常对照组（11．79％）（P〈0．05，OR=1．503）；GD组AA＋CA基因型频率（32．68％）明显高于正常对照组（23．58％）（P〈0．05，OR=1．573）。-857C／T、-238G／A位点等位基因及基因型频率在GD组与正常对照组间的差异均无统计学意义（P〉0．05）。（2）将GD组按性别分组比较，结果显示3个位点的基因型及等位基因频率在男、女性间差异均无统计学意义（P〉0．05）。（3）将早期GD患者按TRAb水平分组比较，结果显示3个位点的等位基因和基因型频率差异均无统计学意义（P〉0．05）。结论TNF-α基因-863C／A单核苷酸多态性可能与安徽地区汉族人群GD的发病具有相关性，而-857c／T、-238G／A位点的单核苷酸多态性与之无相关性；患者早期TRAb水平和GD患者的性别与TNF-α基因-863C／A、-857C／T、-238G／A三个位点的单核苷酸多态性无关联。

Objective To assess the association of tumour necrosis factor-α （TNF—α） gene polymorphisms at positions --863C/A, --857C/T, --238G/A and Graves disease （GD） susceptibility in Chinese Han population in Anhui region. Methods The polymorphisms of TNF—α gene were determined by polymerase chain reaction with specific primers in 254 patients affected with GD and 212 healthy controls. Allelic and genotypic frequencies in GD group and normal controls as well as in different genders were compared. The allelic and genotypic frequencies for different thyroid stimulating hormone receptor antibody （TRAb） levels （TRAb 〉 12 U/L; 〉12 U/L） were also compared among patients with earlier onset GD. Results （1） The A allele at --863C/A locus in GD group （16.73〉） was significantly greater than that of the control group （11.79%） （P〉0.05, OR=1. 503） ; the frequency of AA ＋ CA genotype of --863C/A locus in GD group （32.68 〉 ） was significantly greater than that of control group （23.58 %） （P〉0.05, OR = 1. 573）. There was no significant difference （P〉0.05） in the allelic and genotypic frequencies of --857C/ T, --238G/A loci between the two groups. （2） There was no significant difference （P〉0.05） in the allelic and genotypic frequencies of --863C/A, --857C/T, --238G/A loci between patients of different genders. （3） There was no significant difference （P〉0.05） in such frequencies between patients with earlier onsetGD and different TRAb levels （TRAb 〉12 U/L; 412 U/L）. Conclusion （1） The --863 A allele of TNF- α gene may contribute to the development of GD in Chinese Han population in Anhui, whilst --857C/T, -- 238G/A alleles may not. （2） There is no association between TNF—α gene --863C/A, --857C/T, --238G/ A polymorphisms and development of GD in different genders. （3） There was no association between above polymorphisms and TRAb levels in patients with earlier onset GD.