Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population
Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population
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DOI：
10.1016/j.atherosclerosis.2011.12.009
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发表时间：
2012-03-01
期刊：
影响因子：
5.3
通讯作者：
Pereira, Alexandre C.
中科院分区：
文献类型：
--
作者：
Ferreira, Noely E.;Omae, Samantha;Pereira, Alexandre C.
目的：探讨TXNIP多态性，糖尿病和高血压表型在巴西一般population.Methods：五百七十六个人随机选择的一般城市人口根据MONICA-WHO项目指南之间的关系进行了心血管危险因素的表型。第二，独立的，样本组成的487个家庭，三人组从不同的网站也被选中。研究了9种TXNIP多态性。还探讨了TXNIP变异性与儿童葡萄糖表型之间的潜在关联。结果：TXNIP基因rs7211和rs7212多态性与血糖和血压相关表型显著相关，而与血糖和血压相关表型显著相关。在多变量逻辑回归模型中，研究的标记物即使在调整协变量后仍与糖尿病相关。TXNIP rs7211 T/rs7212 G单倍型（存在于约17%的个体中）与两个样本中的糖尿病显著相关。在儿童中，TXNIP rs7211 T/rs7212 G单倍型与空腹胰岛素浓度相关。结论：TXNIP基因变异携带者TXNIP基因表达水平升高，易发生糖稳态紊乱，易发生糖尿病、高血压等慢性代谢疾病。我们的数据表明，TXNIP基因的遗传变异可能是糖尿病和高血压这两种性状的“共同点”调节剂。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
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.