{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:56:46Z","timestamp":1784915806461,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Higher Education Commission Pakistan","award":["7238\/Sindh\/NRPU\/R"],"award-info":[{"award-number":["7238\/Sindh\/NRPU\/R"]}]},{"name":"Higher Education Commission Pakistan","award":["D\/HEC\/2017"],"award-info":[{"award-number":["D\/HEC\/2017"]}]},{"name":"Dow University of Health Sciences","award":["7238\/Sindh\/NRPU\/R"],"award-info":[{"award-number":["7238\/Sindh\/NRPU\/R"]}]},{"name":"Dow University of Health Sciences","award":["D\/HEC\/2017"],"award-info":[{"award-number":["D\/HEC\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson\u2019s correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases (p &lt; 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia (p &gt; 0.05). Interestingly, control subjects exhibited significantly higher T3 levels (p &lt; 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group (p &lt; 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels.<\/jats:p>","DOI":"10.3390\/ijms25031915","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T05:22:44Z","timestamp":1707110564000},"page":"1915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population"],"prefix":"10.3390","volume":"25","author":[{"given":"Farina","family":"Hanif","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Dow International Medical College, Dow University of Health Sciences, Karachi 74200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2011-8810","authenticated-orcid":false,"given":"Quratulain","family":"Amir","sequence":"additional","affiliation":[{"name":"Dow Institute of Medical Technology, Dow University of Health Sciences, Karachi 74200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Washdev","family":"Washdev","sequence":"additional","affiliation":[{"name":"Dr. Abdul Qadeer Khan Institute of Behavioral Sciences, Dow University of Health Sciences, Karachi 74200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.mce.2017.05.020","article-title":"Comparative approaches to understanding thyroid hormone regulation of neurogenesis","volume":"459","author":"Demeneix","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.psyneuen.2016.08.021","article-title":"Decreased anxiety-and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism","volume":"74","author":"Stohn","year":"2016","journal-title":"Psychoneuroendocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"569147","DOI":"10.1155\/2012\/569147","article-title":"Revisiting thyroid hormones in schizophrenia","volume":"2012","author":"Santos","year":"2012","journal-title":"J. Thyroid Res."},{"key":"ref_4","first-page":"49","article-title":"Inter-Relationship of Thyroid Disorders and Schizophrenia: An Extended Review","volume":"1","author":"Saleem","year":"2015","journal-title":"Pak. J. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.4238\/2015.May.22.10","article-title":"Type II deiodinase polymorphisms and serum thyroid hormone levels in patients with mild cognitive impairment","volume":"14","author":"Luo","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s11064-014-1305-3","article-title":"Level of thyroid-stimulating hormone (TSH) in patients with acute schizophrenia, unipolar depression or bipolar disorder","volume":"39","year":"2014","journal-title":"Neurochem. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/0269881114563634","article-title":"Glutamate and dopamine in schizophrenia: An update for the 21st century","volume":"29","author":"Howes","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.resp.2012.10.004","article-title":"Age and hypothyroidism affect dopamine modulation of breathing and D2 receptor levels","volume":"185","author":"Sykora","year":"2013","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1590\/S1807-59322010000500013","article-title":"Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: A hypothesis","volume":"65","author":"Pereira","year":"2010","journal-title":"Clinics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R83","DOI":"10.1530\/JOE-16-0424","article-title":"Thyroid hormone regulated genes in cerebral cortex development","volume":"232","author":"Bernal","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1210\/jc.2008-1301","article-title":"Common Variation in the DIO2 Gene Predicts Baseline Psychological Well-Being and Response to Combination Thyroxine Plus Triiodothyronine Therapy in Hypothyroid Patients","volume":"94","author":"Panicker","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"590648","DOI":"10.1155\/2012\/590648","article-title":"The link between thyroid function and depression","volume":"2012","author":"Hage","year":"2012","journal-title":"J. Thyroid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"297","DOI":"10.18388\/abp.2015_1002","article-title":"Association of the DIO2 gene single nucleotide polymorphisms with recurrent depressive disorder","volume":"62","author":"Talarowska","year":"2015","journal-title":"Acta Biochim. Pol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.pnpbp.2009.05.003","article-title":"Association of genetic polymorphisms in the type II deiodinase gene with bipolar disorder in a subset of Chinese population","volume":"33","author":"He","year":"2009","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0924-9338(13)76526-X","article-title":"1508\u2013Association study of the dio2 gene as a susceptibility candidate for schizophrenia in the turkish population; A case-control study","volume":"28","author":"Colak","year":"2013","journal-title":"Eur. Psychiatry"},{"key":"ref_16","unstructured":"Seeman, M.V. (2019). Schizophrenia in Women as Compared to Men. Women Psychos. Multidiscip. Perspect., 187."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/inm.12260","article-title":"Factors associated with psychotic relapse in patients with schizophrenia in a Pakistani cohort","volume":"26","author":"Ahmad","year":"2017","journal-title":"Int. J. Ment. Health Nurs."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"125","DOI":"10.5498\/wjp.v8.i5.125","article-title":"Women who suffer from schizophrenia: Critical issues","volume":"8","author":"Seeman","year":"2018","journal-title":"World J. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1111\/bph.14531","article-title":"Oestradiol influences on dopamine release from the nucleus accumbens shell: Sex differences and the role of selective oestradiol receptor subtypes","volume":"176","author":"Yoest","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.yhbeh.2018.04.002","article-title":"Rapid effects of ovarian hormones in dorsal striatum and nucleus accumbens","volume":"104","author":"Yoest","year":"2018","journal-title":"Horm. Behav."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00737-019-00959-3","article-title":"Improvement in depression with oestrogen treatment in women with schizophrenia","volume":"23","author":"Lascurain","year":"2019","journal-title":"Arch. Women\u2019s Ment. Health"},{"key":"ref_22","first-page":"68","article-title":"Spatiotemporal Concentration of Homicides in Karachi","volume":"11","author":"Khan","year":"2019","journal-title":"Pak. J. Criminol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/S0140-6736(13)62036-X","article-title":"Schizophrenia: An integrated sociodevelopmental-cognitive model","volume":"383","author":"Howes","year":"2014","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.biopsych.2017.08.017","article-title":"Heritability of schizophrenia and schizophrenia spectrum based on the nationwide Danish twin register","volume":"83","author":"Hilker","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_25","first-page":"703","article-title":"Genetic liability to schizophrenia is negatively associated with educational attainment in UK Biobank","volume":"25","author":"Menzies","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4103\/IJPSYM.IJPSYM_18_19","article-title":"Perception about marriage among caregivers of patients with schizophrenia and bipolar disorder","volume":"41","author":"Kumar","year":"2019","journal-title":"Indian J. Psychol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/schbul\/sbz041","article-title":"Societal Costs of Schizophrenia in Denmark: A Nationwide Matched Controlled Study of Patients and Spouses Before and After Initial Diagnosis","volume":"46","author":"Hastrup","year":"2019","journal-title":"Schizophr. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4103\/ijsp.ijsp_9_19","article-title":"Effect of marriage on pre-existing psychoses","volume":"35","author":"Behere","year":"2019","journal-title":"Indian J. Soc. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2193","DOI":"10.1097\/MD.0000000000002193","article-title":"Gender and age impacts on the association between thyroid function and metabolic syndrome in Chinese","volume":"94","author":"Meng","year":"2015","journal-title":"Medicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/bdi.12150","article-title":"Gender differences in thyroid system function: Relevance to bipolar disorder and its treatment","volume":"16","author":"Bauer","year":"2014","journal-title":"Bipolar Disord."},{"key":"ref_31","first-page":"em2112","article-title":"Analysing Biochemical Parameters and Developing Risk Prediction Models in Patients with Schizophrenia and Bipolar Disorder","volume":"14","author":"Polat","year":"2021","journal-title":"Electron. J. Med. Educ. Technol."},{"key":"ref_32","unstructured":"Muslim, S., and Khalil, Z. (2000). Effect of Age, Sex, Salt, Water and Climate on T3, T4 and TSH in Healthy Individuals. J. Ayub. Med. Coll, 21."},{"key":"ref_33","unstructured":"Abdel, R. (1992). Developments in Radioimmunoassay and Related Procedures, IAEA."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R123","DOI":"10.1530\/EJE-14-0302","article-title":"Genetics in endocrinology: Genetic variation in deiodinases: A systematic review of potential clinical effects in humans","volume":"171","author":"Verloop","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1210\/mend.15.12.0740","article-title":"Targeted disruption of the type 2 selenodeiodinase gene (DIO 2) results in a phenotype of pituitary resistance to T4","volume":"15","author":"Schneider","year":"2001","journal-title":"Mol. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4103\/0973-0354.183277","article-title":"Serum thyroid stimulating hormone levels and suicidal tendency in patients with first-episode schizophrenia: An exploratory study","volume":"13","author":"Shrivastava","year":"2016","journal-title":"Thyroid Res. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0920-9964(99)00187-5","article-title":"The hypothalamic\u2013pituitary\u2013thyroid axis in patients with schizophrenia","volume":"44","author":"Baumgartner","year":"2000","journal-title":"Schizophr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"620","DOI":"10.3109\/00048679409080785","article-title":"High prevalence of thyroid function test abnormalities in chronic schizophrenia","volume":"28","author":"Othman","year":"1994","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.psychres.2019.02.029","article-title":"Association between thyroid function and metabolic syndrome in male and female schizophrenia patients","volume":"274","author":"Kalinowska","year":"2019","journal-title":"Psychiatry Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jpsychires.2015.11.007","article-title":"Triiodothyronine accelerates and enhances the antipsychotic effect of risperidone in acute schizophrenia","volume":"73","author":"Steibliene","year":"2016","journal-title":"J. Psychiatr. Res."},{"key":"ref_41","first-page":"10","article-title":"A comparative study of Thyroid Hormone levels among the Normal Healthy Persons, Depression and Schizophrenia","volume":"13","author":"Singh","year":"2010","journal-title":"EJP"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1111\/j.1365-2265.2008.03420.x","article-title":"The effect of genetic variation in the type 1 deiodinase gene on the interindividual variation in serum thyroid hormone levels: An investigation in healthy Danish twins","volume":"70","author":"Hansen","year":"2009","journal-title":"Clin. Endocrinol."},{"key":"ref_43","first-page":"312","article-title":"Thyroid hormone levels in chronic schizophrenic patients: Association with psychopathology","volume":"65","author":"Telo","year":"2016","journal-title":"West Indian Med. J"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0278-5846(01)00311-6","article-title":"Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients","volume":"26","author":"Yazici","year":"2002","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.pnpbp.2012.06.008","article-title":"Triiodothyronine may be possibly associated with better cognitive function and less extrapyramidal symptoms in chronic schizophrenia","volume":"39","author":"Ichioka","year":"2012","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_46","first-page":"43","article-title":"The genetics study of gestational diabetes in Iranian women and DIO2 gene","volume":"2","author":"Asadi","year":"2016","journal-title":"Mol. Med. J."},{"key":"ref_47","first-page":"557","article-title":"The nosology of schizophrenia: Toward DSM-5 and ICD-11","volume":"35","author":"Tandon","year":"2012","journal-title":"Psychiatr. Clin."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1915\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:55:06Z","timestamp":1760104506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/3\/1915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,5]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["ijms25031915"],"URL":"https:\/\/doi.org\/10.3390\/ijms25031915","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,5]]}}}