CTLA-4基因外显子4区AT重复序列多态性及碘摄入量与Graves病的相关性研究  

Association of AT repeats polymorphism in the exon 4 rigion of the CTLA-4,iodine intake and Graves disease

作　　者：陈晓铭[1] 武革[1] 郭中秋[2] 周飞[1] 吴美芬[1] 

机构地区：[1]广东医学院附属医院内分泌科,广东湛江524001 [2]深圳市龙岗区人民医院,广东深圳518172

出　　处：《解剖学研究》2011年第4期281-284,共4页Anatomy Research

基　　金：广东省自然科学基金(A06028968);湛江市科技攻关项目(2008C02003)

摘　　要：目的探讨细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)基因第4外显子区AT重复序列多态性多态性[CTLA-4(AT)n]及碘摄入状况与粤西汉族人Graves病(Graves disease,GD)发病的相关性。方法收取2006年门诊及住院患者中初诊为GD102例和正常对照组100例,应用PCR-SSLP确定其CTLA-4基因第4外显子区3′末端AT重复序列的基因型,应用砷铈催化分光光度法测定其尿碘含量。结果①CTLA-4基因第4外显子区3′末端(AT)重复序列的等位基因有19种,GD组中106bp等位基因频率占24.50%,正常对照组中占18.50%,GD组较高,但其差异无统计学意义(χ2=2.159,P=0.142)。②GD组尿碘中位数为305.50μg/L,正常对照组尿碘中位数为263.51μg/L,两组比较差异有统计学意义(Z=-2.558,P=0.011)。③尿碘大于300μg/L且携带有106bp等位基因的人群中,患GD的有29人(54.70%),尿碘大于300μg/L的而未携带有106bp的人群中患GD的有24人(45.30%),经卡方检验两组数据比较其差异有统计学意义(χ2=4.425,P=0.035),携带有106bp等位基因的人群其尿碘大于300μg/L时其患GD的风险为不携带106bp的人群的2.658倍。结论 CTLA-4(AT)n多态性作为单一因素其可能与GD无相关性。粤西沿海地区GD患者其碘摄入量高于正常人。具有CTLA-4外显子3′末端为106bp的人群同时伴过量的碘摄入其GD患病率较高。Objective To investigate association of AT repeats polymorphism in the 3 untranslated region of the exon 4 of cytotoxic T lymphocyte associated antigen-4（CTLA-4（AT） n）,iodine intake and Graves disease a among the Hans in western of Guangdong.Methods The CTLA-4（AT） n polymorphisms were genotyped via PCR-RFLP and the urinary iodine was measured by spectrophotometer in 102 GD patients and 100 healthy controls.Results ① There were 19 allele genes in the 3 untranslated region of CTLA-4,the same to control subjects.The frequency of 106 bp allele was 24.50% in GD and 18.50% in the control.There was no significant difference between two groups.（χ2=2.159,P=0.142）.Compared with the other groups with the controls also given the same conclusions（P0.05）.②The median of urine iodine is 305.50μg/L in GD patients and 263.51 μg/L in healthy controls.There was significant difference between the two groups（Z=-2.558,P=0.011）.③There were 29（54.70%） patients with GD among people which urinary iodine was greater than 300 g/L and carrying the 106 bp allele,while 24 patients with GD（45.30%） among people whose urinary iodine was higher than 300 μg/L without carrying 106 bp.The difference was significant by the chi-square test to compare the two data（χ2=4.425,P=0.035）.The risk of GD for people who carried the 106 bp allele was 2.658（95%CI 1.057,6.688） times higher than the people without carrying 106 bp when their urine iodine was over 300 μg/L.Conclusion ② CTLA-4（AT） n gene may not be susceptible gene to Graves disease among the Hans in the western Guangdong.The intake of iodine was higher among the population along coastal district in Western Guangdong,which indicated that iodine might be a risk factor in the pathogenesis of Graves disease.Excessive iodine intake can induce the prevalence of GD to shift from recessive to dominant among the patients with the 106bp repeats in 3＇ end of exon 4 of CTLA-4.

关 键 词：GRAVES病 遗传易感性 细胞毒性T淋巴细胞相关抗原-4 尿碘 砷铈反应 

分 类 号：R581.1[医药卫生—内分泌]