TNFRSF1A多态性与自身免疫性甲状腺疾病的相关性

目的评估黑龙江省齐齐哈尔地区汉族人群自身免疫性甲状腺病(autoimmune thyroid disease,AITD)与TNFRSF1A基因单核苷酸多态性(SNPs)rs4149576、rs4149577、rs4149570、rs1800693及rs767455的相关性。方法收集659例对照组和587例AITD患者,其中桥本甲状腺炎(HT)患者214例和Graves病(GD)患者373例。按照年龄和性别进行匹配。采用聚合酶链式反应(PCR)及连接酶检测反应(LDR)对rs4149576、rs4149577、rs4149570、rs1800693和rs767455进行基因分型,通过Haploview4.0计算SNPs的单倍型频率。同时,评估AITD与对照之间基因型和等位基因分布的95%置信区间(95%CI)比值比(OR)。将年龄和性别作为调节调整变量,通过多元逻辑回归模型计算调整ORs。结果 AITD患者与对照组TNTSSF1A基因中所有5个SNPs,等位基因和基因型分布均未发现显著差异(均P>0.05)。进一步分析HT、GD患者与对照组5个TNFRSF1A SNPs等位基因和基因型频率均未发现显著差异(均P>0.05)。单倍型分析发现ACGTT在AITD和对照组中最为常见。但其单倍型分布不存在显著差异。调整年龄和性别前,TNFRSF1A基因5个SNPs均与GD和HT无关(均P>0.05);调整年龄和性别后,只有rs4149570多态性与HT轻度相关[OR(95%CI)=1.41(1.05-1.94),P=0.032]。有/无眼病GD患者TNFRSF1A基因多态性等位基因和基因型频率无显著差异(均P>0.05)。结论 TNFRSF1A基因中5个SNPs与中国汉族人群AITD无关,但在调整性别和年龄后rs4149570显示与HT存在微弱相关性。

Association between TNFRSF1A polymorphism and autoimmune thyroid disease

Foreign reports indicate that TNFRS-F1 A polymorphism is closely related to the pathogenesis of autoimmune thyroid disease(AITD), while the relationship between TNFRSF1 A polymorphism and AITD in Chinese Han population remains obscure. In this study, the association between AITD and five single nucleotide polymorphisms(SNPs) including rs4149576, rs4149577, rs4149570, rs1800693 and rs767455 was determined in Chinese Han population of Qiqihar. Total of 659 healthy controls and 587 AITD patients, including 214 patients with Hashimoto’s thyroiditis(HT) and 373 patients with Graves’ disease(GD), were enrolled and matched by age and gender. Genotyping of rs4149576, rs4149577, rs4149570, rs1800693 and rs767455 was conducted by polymerase chain reaction(PCR) and ligase detection reaction(LDR), and the haplotype frequencies of SNPs were calculated by Haploview 4.0. Meanwhile, the 95% confidence interval(95% CI) and odds ratio(OR) of genotype and allele distribution between AITD and healthy controls were calculated, while ORs were calculated by multivariate logistic regression model with age and gender as adjustment variables. Data indicated that there was no significant difference in the allele and genotype frequencies between AITD patients and healthy controls in any of the five SNPs in TNFRSF1 A gene(P>0.05), and further analysis showed that HT or GD patients and healthy controls either had no difference in the allele and genotype frequencies of the five SNPs in TNFRSF1 A gene(P>0.05).Haplotype analysis revealed that ACGTT was most common in AITD and healthy controls. However, there was no significant difference in haplotype distribution. Before the adjustment of age and gender, all the 5 SNPs of TNFRSF1 A gene were unrelated to GD and HT(P>0.05). After the adjustment, only rs4149570 polymorphism was mildly correlated with HT [OR(95%CI)=1.41(1.05-1.94), P=0.032]. The allele and genotype frequencies of TNFRSF1 A gene polymorphism had no difference among GD patients with or without eye diseases(P>0.05). In conclusion, five SNPs in TNFRSF1 A gene are not related to AITD in Chinese Han population, but rs4149570 shows a weak correlation with HT after adjusting gender and age.