title: Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans.
abstract: BACKGROUND
  Genetic variation at the transcription factor 7-like 2 locus has been linked to type 2 diabetes in predominantly European-derived populations. The biological basis of these associations remains to be determined.
  
  
  OBJECTIVE
  The objective of this study was to evaluate previously associated variants for association with measures of glucose homeostasis in Hispanic-Americans and African-Americans and determine the biological mechanism(s) through which these variants exert their effect.
  
  
  METHODS
  This study was the Insulin Resistance Atherosclerosis Family Study (IRAS-FS).
  
  
  METHODS
  The IRAS-FS is a community-based study of Hispanic-Americans (San Antonio, TX, and San Luis Valley, CO) and African-Americans (Los Angeles, CA).
  
  
  METHODS
  A total of 1040 Hispanic-American and 500 African-American individuals from the IRAS-FS formed the basis of this study. MAIN OUTCOMES MEASURES(S): The primary glucose homeostasis phenotypes of interest in this study were derived from the frequently sampled iv glucose tolerance test and include insulin sensitivity, acute insulin response, and disposition index.
  
  
  RESULTS
  In Hispanic-Americans, significant evidence of association was observed between single-nucleotide polymorphisms rs7903146 and rs112255372 with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (P = 0.032 and 0.036, respectively). Other quantitative measures, e.g. insulin sensitivity or disposition index, were not associated with the single nucleotide polymorphisms examined. In African-Americans there was no evidence of association observed.
  
  
  CONCLUSIONS
  These results suggest that transcription factor 7-like 2 variants could play a role in the pathogenesis of type 2 diabetes in the Hispanic-American population through a mechanism involving insulin secretion.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Allison B
authors.initials: AB
authors.lastname: Lehtinen
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Joel K
authors.initials: JK
authors.lastname: Campbell
authors.forename: Steven M
authors.initials: SM
authors.lastname: Haffner
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000328:Adult; D001741:Black or African American; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005951:Glucose Tolerance Test; D006630:Hispanic or Latino / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D001786:Blood Glucose; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein