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目的:研究中国北方汉族弥漫性毒性甲状腺肿(GD)患者细胞毒性T淋巴细胞相关抗原4(CTLA-4)第1外显子49位点A/G多态性与抗甲状腺药物(ATD)所致白细胞减少的相关性。方法:收集2009年10月至2010年6月到青岛大学医学院附属医院内分泌科就诊的GD患者(GD组)和同期到体检中心查体的健康人群(健康对照组)。GD组分为3个亚组:ATD治疗后白细胞减少组、ATD治疗后白细胞正常组和ATD治疗前白细胞减少组。收集所有研究对象外周非抗凝静脉血血凝块,提取基因组DNA,应用聚合酶链反应-限制性片段长度多态性技术测定CTLA-4基因第1外显子49位点基因型,抽取部分样本进行测序,并计算各组的基因型和等位基因频率。结果:GD组211例患者(ATD治疗后白细胞减少组73例,ATD治疗后白细胞正常组86例,GD合并白细胞减少组52例)、健康对照组85例纳入研究。GD组CTLA-4基因第1外显子49位点AA、AG和GG基因型频率分别为2.4%(5例)、38.8%(82例)、58.8%(124例),A、G等位基因频率分别为21.8%、78.2%;健康对照组AA、AG和GG的基因型频率分别为15.3%(13例)、32.9%(28例)和51.8%(44例),A和G的等位基因频率分别为31.8%和68.2%;2组的基因型和等位基因频率差异有统计学意义(χ~2=17.74,P=0.000 1;χ~2=6.48,P=0.01)。CTLA-4基因第1外显子49位点基因型和等位基因频率在ATD治疗后白细胞减少组、ATD治疗后白细胞正常组和GD合并白细胞减少组之间差异均无统计学意义(均P>0.05)。结论:中国北方汉族人群GD发病与CTLA-4基因第1外显子49位点A/G多态性相关,而ATD导致的白细胞减少似乎与其多态性无关。
Objective: To investigate the relationship between the A / G polymorphism at exon 49 of ATLA-4 and anti-thyroid drug (ATD) in patients with diffuse toxic goiter (GD) in North China. Related to leukopenia. Methods: The GD patients (GD group) and the healthy people (healthy control group) who went to the physical examination center in the same period were collected from October 2009 to June 2010 in the Department of Endocrinology, Affiliated Hospital of Qingdao University Medical College. GD group was divided into three subgroups: leukopenia group after ATD treatment, normal leukocyte group after ATD treatment and leukopenia group before ATD treatment. All the subjects were collected peripheral non-anticoagulant venous blood clotting, genomic DNA extraction, polymerase chain reaction - restriction fragment length polymorphism was used to detect CTLA-4 gene exon 49 49 locus genotypes, extraction part Samples were sequenced and genotype and allele frequencies were calculated for each group. Results: A total of 211 patients in the GD group (73 leukopenia patients after ATD treatment, 86 normal leukocyte patients after ATD treatment and 52 leukemia patients with GD) and 85 healthy controls were included in the study. The frequencies of AA, AG and GG genotypes in 49 loci of exon 1 of CTLA-4 gene in GD group were 2.4% (5 cases), 38.8% (82 cases), 58.8% (124 cases), A and G The genotype frequencies of AA, AG and GG were 15.3% (13 cases), 32.9% (28 cases) and 51.8% (44 cases) in healthy controls, respectively The frequencies of genotype and allele were 31.8% and 68.2% respectively in the two groups (χ ~ 2 = 17.74, P = 0.0001; χ ~ 2 = 6.48, P = 0.01). There was no significant difference in genotype and allele frequencies of CTLA-4 gene 49 locus between ATD-treated leukopenia group, ATD-treated leukocyte-normal group and GD-combined leukopenia group (all P > 0.05). CONCLUSIONS: The incidence of GD in Chinese Han population in northern China correlates with the A / G polymorphism at locus 49 of exon 1 of CTLA-4 gene. The leukopenia caused by ATD seems to be unrelated to its polymorphism.