title: Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Noely E
authors.initials: NE
authors.lastname: Ferreira
authors.forename: Samantha
authors.initials: S
authors.lastname: Omae
authors.forename: Abel
authors.initials: A
authors.lastname: Pereira
authors.forename: Mariliza V
authors.initials: MV
authors.lastname: Rodrigues
authors.forename: Ayumi A
authors.initials: AA
authors.lastname: Miyakawa
authors.forename: Luciene C G
authors.initials: LC
authors.lastname: Campos
authors.forename: Paulo C J L
authors.initials: PC
authors.lastname: Santos
authors.forename: Luiz A
authors.initials: LA
authors.lastname: Dallan
authors.forename: Tânia L
authors.initials: TL
authors.lastname: Martinez
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.forename: José G
authors.initials: JG
authors.lastname: Mill
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000235:genetics; D001938:Brazil; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D016014:Linear Models; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; C486715:TXNIP protein, human