Type 2 Deiodinase Thr92Ala Polymorphism Is Not Associated With Arterial Hypertension in Type 2 Diabetes Mellitus Patients
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.5
Since 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 Funding
Grant support was provided by Conselho Nacional de Desenvolvimento Científico e Technológico (CNPq), Brazil.
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