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 glucosephenotypes
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