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Type 2 Deiodinase Thr92Ala Polymorphism Is Not Associated With Arterial Hypertension in Type 2 Diabetes Mellitus Patients
2007; Lippincott Williams & Wilkins; Volume: 49; Issue: 6 Linguagem: Inglês
10.1161/hypertensionaha.107.088278
ISSN1524-4563
AutoresLuís Henrique Santos Canani, Murilo Anderson Leie, Walter Escouto Machado, Clarissa Capp, Ana Luiza Maia,
Tópico(s)Diabetes Treatment and Management
ResumoHomeHypertensionVol. 49, No. 6Type 2 Deiodinase Thr92Ala Polymorphism Is Not Associated With Arterial Hypertension in Type 2 Diabetes Mellitus Patients Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBType 2 Deiodinase Thr92Ala Polymorphism Is Not Associated With Arterial Hypertension in Type 2 Diabetes Mellitus Patients Luís Henrique Canani, Murilo A. Leie, Walter Escouto Machado, Clarissa Capp and Ana Luiza Maia Luís Henrique CananiLuís Henrique Canani Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil , Murilo A. LeieMurilo A. Leie Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil , Walter Escouto MachadoWalter Escouto Machado Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil , Clarissa CappClarissa Capp Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil and Ana Luiza MaiaAna Luiza Maia Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Originally published26 Mar 2007https://doi.org/10.1161/HYPERTENSIONAHA.107.088278Hypertension. 2007;49:e47Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 26, 2007: Previous Version 1 To the Editor:A single nucleotide polymorphism in Type 2 deodinase (Dio2) gene (A/G) in humans, in which a threonine (Thr) changes to alanine (Ala) at codon 92 (Thr92Ala), has been associated with a lower glucose disposal rate and higher insulin resistance in type 2 diabetes (DM2) patients.1,2 Nevertheless, these findings were not replicated in larger studies.3,4 Recently, Gumieniak et al reported that the Ala allele increases the risk for development of arterial hypertension.5Since insulin resistance can cause hypertension, we sought to extend our previous original observation and evaluate the association of the Thr92Ala polymorphism with hypertension. DM2 patients were submitted to a standard questionnaire, physical examination, and laboratory tests that included Thr92Ala genotyping, as previously described.1 Blood pressure was measured twice in the sitting position after a 10-minute rest by means of a mercury sphygmomanometer (Korotkoff phases I and V). Hypertension was defined as blood pressure ≥140/90 mm Hg or antihypertensive drug treatment. Patients with elevated serum creatinine (>1.5 mg/dL [132.6 mmol/L]) or using insulin were excluded. DNA from 315 DM2 patients was analyzed (57% women; 68% white, mean age 59 years). The genotypes were in Hardy-Weinberg equilibrium and the frequency of Ala allele (0.41) was similar to that described by Gumieniak et al.5 Confirming our previous observation, patients homozygous for the Ala allele present higher insulin resistance than those with ThrAla or ThrThr genotypes (homeostasis model assessment 7.78 [0.88 to 28.2] versus 4.75 [0.3 to 30.2], P=0.014). However, no differences were observed in the prevalence of hypertension among the genotypes (AlaAla, ThrAla, ThrThr; 76.4%, 79.1%, 75.7%, P=0.785). The mean systolic (142±21, 144±25, 144±22 mm Hg, P=0.880) or diastolic (85±12, 87±15, 85±12 mm Hg, P=0.256) blood pressure values were also similar. These results did not change when analyzing only white subjects.These apparently conflicting findings might be partially explained by differences in the studied population. In Gumieniak's report, DM2 patients were excluded and subjects were younger than those in our sample. Another major difference refers to the definition of hypertension. We used the World Health Organization definition of hypertension, and all subjects were evaluated on their regular medications. In Gumieniak's report,5 antihypertensive medications were suspended for 2 to 4 weeks, the cut-offs for hypertension were different from the usual, and severe forms of hypertension were excluded. In conclusion, the DIO2 Thr92Ala polymorphism is associated with lower insulin sensitivity, but it is not a major determinant of blood pressure levels or hypertension in DM2 patients.Source of FundingGrant support was provided by Conselho Nacional de Desenvolvimento Científico e Technológico (CNPq), Brazil.DisclosuresNone.1 Canani LH, Capp C, Dora JM, Meyer EL, Wagner MS, Harney JW, Larsen PR, Gross JL, Bianco AC, Maia AL. The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2005; 90: 3472–3478.CrossrefMedlineGoogle Scholar2 Mentuccia D, Proietti-Pannunzi L, Tanner K, Bacci V, Pollin TI, Poehlman ET, Shuldiner AR, Celi FS. Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes. 2002; 51: 880–883.CrossrefMedlineGoogle Scholar3 Grarup N, Andersen MK, Andreasen CH, Albrechtsen A, Borch-Johnsen K, Jorgensen T, Auwerx J, Schmitz O, Hansen T, Pedersen O. Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects. J Clin Endocrinol Metab. 2007; 92: 363–366.CrossrefMedlineGoogle Scholar4 Maia AL, Dupuis J, Manning A, Liu C, Meigs JB, Cupples LA, Larsen PR, Fox CS. The type 2 deiodinase (DIO2) A/G polymorphism is not associated with glycemic traits: the Framingham Heart Study. Thyroid. 2007; In press.Google Scholar5 Gumieniak O, Perlstein TS, Williams JS, Hopkins PN, Brown NJ, Raby BA, Williams GH. Ala92 Type 2 deiodinase allele increases risk for the development of hypertension. Hypertension. 2007; 49: 461–466.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Wang X, Chen K, Zhang C, Wang H, Li J, Wang C, Teng W, Shan Z, Lai Y and Abbara A (2021) The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Higher Body Mass Index and Fasting Glucose Levels: A Systematic Review and Meta-Analysis, BioMed Research International, 10.1155/2021/9914009, 2021, (1-8), Online publication date: 7-Oct-2021. Russo S, Salas-Lucia F and Bianco A (2021) Deiodinases and the Metabolic Code for Thyroid Hormone Action, Endocrinology, 10.1210/endocr/bqab059, 162:8, Online publication date: 1-Aug-2021. Bianco A, Dumitrescu A, Gereben B, Ribeiro M, Fonseca T, Fernandes G and Bocco B (2019) Paradigms of Dynamic Control of Thyroid Hormone Signaling, Endocrine Reviews, 10.1210/er.2018-00275, 40:4, (1000-1047), Online publication date: 1-Aug-2019. Medici M, Visser W, Visser T and Peeters R (2015) Genetic Determination of the Hypothalamic-Pituitary-Thyroid Axis: Where Do We Stand?, Endocrine Reviews, 10.1210/er.2014-1081, 36:2, (214-244), Online publication date: 1-Apr-2015. 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Shih P and O'Connor D (2008) Hereditary Determinants of Human Hypertension, Hypertension, 51:6, (1456-1464), Online publication date: 1-Jun-2008.Maia A, Hwang S, Levy D, Larson M, Larsen P and Fox C (2008) Lack of Association Between the Type 2 Deiodinase A/G Polymorphism and Hypertensive Traits: The Framingham Heart Study, Hypertension, 51:4, (e22-e23), Online publication date: 1-Apr-2008. Shih P, O'Connor D and Mahata S (2008) Human Genomics in Hypertension Genomics, 10.3109/9781420067064-11, (223-245), Online publication date: 9-Oct-2008. Gumieniak O and Williams G (2007) Response to Type 2 Deiodinase Thr92Ala Polymorphism Is Not Associated With Arterial Hypertension in Type 2 Diabetes Mellitus Patients, Hypertension, 49:6, (e48-e48), Online publication date: 1-Jun-2007. Berta E, Lengyel I, Halmi S, Zrínyi M, Erdei A, Harangi M, Páll D, Nagy E and Bodor M (2019) Hypertension in Thyroid Disorders, Frontiers in Endocrinology, 10.3389/fendo.2019.00482, 10 June 2007Vol 49, Issue 6 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.107.088278PMID: 17389255 Originally publishedMarch 26, 2007 PDF download Advertisement SubjectsClinical StudiesDiabetes, Type 2EtiologyGenetics
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