在一项基于人群的研究中,TPO基因变异和甲状腺过氧化物酶抗体血清转化之间的纵向关联:德黑兰甲状腺研究。

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Genetic testing and molecular biomarkers Pub Date : 2023-03-01 DOI:10.1089/gtmb.2022.0122
Amir Hossein Ghanooni, Azita Zadeh-Vakili, Boshra Rezvankhah, Somayeh Jafari Nodushan, Mahdi Akbarzadeh, Atieh Amouzegar, Maryam S Daneshpour, Davood Khalili, Yadollah Mehrabi, Seyed Alireza Ebadi, Fereidoun Azizi
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引用次数: 0

摘要

自身免疫性甲状腺疾病(AITD)通常伴有抗甲状腺抗体,可作为早期预测指标。本研究旨在探讨甲状腺过氧化物酶(TPO)基因变异与TPOAb存在之间的关系,并评估与TPOAb阴性向TPOAb阳性血清转化相关的环境因素的影响。方法:根据TPOAb阳性及其与TPO基因内53个单核苷酸多态性(snp)的关系(横断面法)评估德黑兰甲状腺研究1期和2期参与者(n = 5327,≥20岁)。tpoab阴性参与者(n = 4815)随访5.5年进行血清转换。评估TPO基因变异与TPOAb血清转化之间的关系(纵向方法)。结果:横断期tpoab阳性521例,随访期间新增tpoab阳性266例。经过质量控制(Hardy-Weinberg平衡(p -5)和次要等位基因频率< 0.05),49个snp符合关联分析的条件。从这组snp中鉴定出14个与TPOAb阳性相关的snp。在横断面和纵向分析中,位于3'UTR TPO基因的rs6605278与该变异的相关性最为显著,并且在调整了年龄、性别、体重指数(BMI)、吸烟、胎次和口服避孕药消费等因素后仍保持相关性(p结论:tpoab阳性可以部分解释TPO基因的变异。新的与tpoab相关的snp在伊朗作为一个种族多样化的人群中被观察到。
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Longitudinal Associations Between TPO Gene Variants and Thyroid Peroxidase Antibody Seroconversion in a Population-Based Study: Tehran Thyroid Study.

Introduction: Autoimmune thyroid diseases (AITD) are usually accompanied by anti-thyroid antibodies which can serve as early predictive markers. This study was designed to investigate the relationship between thyroid peroxidase (TPO) gene variants and the presence of TPOAb and to evaluate the effect of environmental factors associated with seroconversion from TPOAb-negative to TPOAb-positive. Methods: Participants from phases 1 and 2 of the Tehran Thyroid Study in (n = 5327, ≥20 years) were evaluated in terms of TPOAb positivity, and its relationship with 53 single nucleotide polymorphisms (SNPs) from within the TPO gene (cross-sectional approach). TPOAb-negative participants (n = 4815) were followed up for seroconversion for 5.5 years. The relationship between the TPO gene variants and the TPOAb seroconversion was evaluated (longitudinal approach). Results: There were 521 TPOAb-positive participants in the cross-sectional phase and 266 new TPOAb-positive cases observed during the follow-up period. After quality control (Hardy-Weinberg equilibrium (p < 1 × 10-5) and minor allele frequency < 0.05), 49 SNPs were qualified for association analyses. From this set fourteen SNPs were identified that were associated with TPOAb positivity. rs6605278, located in the 3'UTR TPO gene, was the most highly significantly associated of the variant and remained associated after adjustment for age, gender, body mass index (BMI), smoking, number of parity, and oral contraceptive consumption in both cross-sectional and longitudinal analyses (p < 0.05). Conclusions: TPOAb-positivity can be partially explained by variants in the TPO gene. New TPOAb-associated SNPs were observed in Iranians as an ethnically diverse population.

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来源期刊
CiteScore
2.50
自引率
7.10%
发文量
63
审稿时长
1 months
期刊介绍: Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results. Genetic Testing and Molecular Biomarkers coverage includes: -Diagnosis across the life span- Risk assessment- Carrier detection in individuals, couples, and populations- Novel methods and new instrumentation for genetic testing- Results of molecular, biochemical, and cytogenetic testing- Genetic counseling
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