title: GLUT4 gene polymorphisms and their association with type 2 diabetes in south Indians.
abstract: OBJECTIVE
  The GLUT4 gene, which encodes glucose transporter 4, is a candidate gene for type 2 diabetes mellitus (T2DM). The aim of this study was to screen the GLUT4 gene for polymorphisms and to study association of such polymorphisms with T2DM in an Asian Indian population in southern India.
  
  
  METHODS
  The GLUT4 gene was sequenced in 25 normal glucose tolerance (NGT) and 25 T2DM subjects, and the variants found were then genotyped by polymerase chain reaction-restriction fragment length polymorphism in a pilot study population of 552 NGT and 643 T2DM subjects, randomly selected from the Chennai Urban Rural Epidemiology Study. Two of the variants (rs5435 and the novel variant), which showed significantly higher minor allele frequency in T2DM compared with NGT individuals in the pilot study population, were then retested with an additional 465 NGT and 363 T2DM subjects, giving a final sample size of 1,017 NGT and 1,006 T2DM subjects.
  
  
  RESULTS
  Sequencing of the GLUT4 gene revealed three known polymorphisms (rs5418, rs5421, and rs5435) and one novel T→G variant in the 3' untranslated region (UTR) at nucleotide position 6787483. The rs5418 and rs5421 polymorphisms did not show any association with diabetes. The rs5435 [Asn130Asn(C→T)] polymorphism was found to be associated with diabetes, with the odds ratio for the CT+TT genotype being 1.26 (95% confidence interval, 1.00-1.57; P=0.043) when the CC genotype was taken as reference. The frequency of the TG genotype of the novel 3'UTR T→G variant was significantly higher in diabetes subjects (1%) compared with NGT subjects (0.2%) (P=0.021). There was a significant difference in the proportion of the ACGT haplotype of the rs5418(A→G), rs5435(C→T), rs5421(C→G), and the T→G 3'UTR variant between the NGT (7.5%) and diabetes (5%) groups (P=0.003).
  
  
  CONCLUSIONS
  The rs5435 (C→T) polymorphism of the GLUT4 gene is associated with type 2 diabetes in this south Indian population.
authors.affiliation: Madras Diabetes Research Foundation, ICMR Advanced Centre for Genomics of Type 2 Diabetes, Chennai, India.
authors.forename: Dhanasekaran
authors.initials: D
authors.lastname: Bodhini
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Radha
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Partha P
authors.initials: PP
authors.lastname: Majumder
authors.forename: M R Satyanarayana
authors.initials: MR
authors.lastname: Rao
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D051275:Glucose Transporter Type 4 / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D020413:3' Untranslated Regions; D051275:Glucose Transporter Type 4; C495692:SLC2A4 protein, human