{"title":"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。","authors":"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","doi":"10.1089/gtmb.2022.0122","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Introduction:</i></b> 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 (<i>TPO</i>) gene variants and the presence of TPOAb and to evaluate the effect of environmental factors associated with seroconversion from TPOAb-negative to TPOAb-positive. <b><i>Methods:</i></b> Participants from phases 1 and 2 of the Tehran Thyroid Study in (<i>n</i> = 5327, ≥20 years) were evaluated in terms of TPOAb positivity, and its relationship with 53 single nucleotide polymorphisms (SNPs) from within the <i>TPO</i> gene (cross-sectional approach). TPOAb-negative participants (<i>n</i> = 4815) were followed up for seroconversion for 5.5 years. The relationship between the <i>TPO</i> gene variants and the TPOAb seroconversion was evaluated (longitudinal approach). <b><i>Results:</i></b> 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 (<i>p</i> < 1 × 10<sup>-5</sup>) 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 <i>TPO</i> 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 (<i>p</i> < 0.05). <b><i>Conclusions:</i></b> TPOAb-positivity can be partially explained by variants in the <i>TPO</i> gene. New TPOAb-associated SNPs were observed in Iranians as an ethnically diverse population.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Longitudinal Associations Between <i>TPO</i> Gene Variants and Thyroid Peroxidase Antibody Seroconversion in a Population-Based Study: Tehran Thyroid Study.\",\"authors\":\"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\",\"doi\":\"10.1089/gtmb.2022.0122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Introduction:</i></b> 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 (<i>TPO</i>) gene variants and the presence of TPOAb and to evaluate the effect of environmental factors associated with seroconversion from TPOAb-negative to TPOAb-positive. <b><i>Methods:</i></b> Participants from phases 1 and 2 of the Tehran Thyroid Study in (<i>n</i> = 5327, ≥20 years) were evaluated in terms of TPOAb positivity, and its relationship with 53 single nucleotide polymorphisms (SNPs) from within the <i>TPO</i> gene (cross-sectional approach). TPOAb-negative participants (<i>n</i> = 4815) were followed up for seroconversion for 5.5 years. The relationship between the <i>TPO</i> gene variants and the TPOAb seroconversion was evaluated (longitudinal approach). <b><i>Results:</i></b> 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 (<i>p</i> < 1 × 10<sup>-5</sup>) 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 <i>TPO</i> 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 (<i>p</i> < 0.05). <b><i>Conclusions:</i></b> TPOAb-positivity can be partially explained by variants in the <i>TPO</i> gene. New TPOAb-associated SNPs were observed in Iranians as an ethnically diverse population.</p>\",\"PeriodicalId\":12603,\"journal\":{\"name\":\"Genetic testing and molecular biomarkers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetic testing and molecular biomarkers\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/gtmb.2022.0122\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic testing and molecular biomarkers","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/gtmb.2022.0122","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.
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