Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population


Autoria(s): Ferreira, Noely E.; Omae, Samantha; Pereira, Abel; Rodrigues, Mariliza V.; Miyakawa, Ayumi A.; Campos, Luciene C. G.; Santos, Paulo C. J. L.; Dallan, Luiz A.; Martinez, Tania L.; Santos, Raul D.; Mill, Jose G.; Krieger, Jose E.; Pereira, Alexandre C.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

14/10/2013

14/10/2013

01/03/2012

Resumo

Objective: To investigate the relationship between TXNIP polymorphisms, diabetes and hypertension phenotypes in the Brazilian general population. Methods: Five hundred seventy-six individuals randomly selected from the general urban population according to the MONICA-WHO project guidelines were phenotyped for cardiovascular risk factors. A second, independent, sample composed of 487 family-trios from a different site was also selected. Nine TXNIP polymorphisms were studied. The potential association between TXNIP variability and glucose-phenotypes in children was also explored. TXNIP expression was quantified by real-time PCR in 53 samples from human smooth muscle cells primary culture. Results: TXNIP rs7211 and rs7212 polymorphisms were significantly associated with glucose and blood pressure related phenotypes. In multivariate logistic regression models the studied markers remained associated with diabetes even after adjustment for covariates. TXNIP rs7211 T/rs7212 G haplotype (present in approximately 17% of individuals) was significantly associated to diabetes in both samples. In children, the TXNIP rs7211 T/rs7212 G haplotype was associated with fasting insulin concentrations. Finally, cells harboring TXNIP rs7212 G allele presented higher TXNIP expression levels compared with carriers of TXNIP rs7212 CC genotype (p = 0.02). Conclusion: Carriers of TXNIP genetic variants presented higher TXNIP expression, early signs of glucose homeostasis derangement and increased susceptibility to chronic metabolic conditions such as diabetes and hypertension. Our data suggest that genetic variation in the TXNIP gene may act as a "common ground" modulator of both traits: diabetes and hypertension. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [01-00009-0]

Prefeitura de Vitoria/Facitec

Prefeitura de Vitoria/Facitec

Identificador

ATHEROSCLEROSIS, CLARE, v. 221, n. 1, pp. 131-136, MAR, 2012

0021-9150

http://www.producao.usp.br/handle/BDPI/35084

10.1016/j.atherosclerosis.2011.12.009

http://dx.doi.org/10.1016/j.atherosclerosis.2011.12.009

Idioma(s)

eng

Publicador

ELSEVIER IRELAND LTD

CLARE

Relação

ATHEROSCLEROSIS

Direitos

closedAccess

Copyright ELSEVIER IRELAND LTD

Palavras-Chave #DIABETES #HYPERTENSION #TXNIP #POLYMORPHISM #OXIDATIVE STRESS #BLOOD-PRESSURE #SHEAR-STRESS #GLUCOSE #CELLS #TXNIP #METABOLISM #EXPRESSION #HEART #PERIPHERAL VASCULAR DISEASE
Tipo

article

original article

publishedVersion