title: Association of His1085His INSR gene polymorphism with type 2 diabetes in South Indians.
abstract: OBJECTIVE
  The INSR gene, which encodes the insulin receptor, is a candidate gene for type 2 diabetes (T2D). The objective of the present study was to sequence some of the crucial exons in the INSR gene such as exon 2, which encodes the insulin-binding domain of the INSR protein, and exons 17-21, which encode the protein tyrosine kinase domain for mutations/polymorphisms, and to study their association with T2D in the South Indian population.
  
  
  METHODS
  The INSR gene was sequenced in 25 normal glucose-tolerant (NGT) and 25 T2D subjects, and the variant found was genotyped by polymerase chain reaction-restriction fragment length polymorphism in 1,016 NGT and 1,010 T2D subjects, randomly selected from the Chennai Urban Rural Epidemiology Study.
  
  
  RESULTS
  Only one previously reported polymorphism, His1085His [rs1799817, (C→T)], in exon 17 was detected by sequencing. The frequency of the "T" allele of the His1085His polymorphism was significantly lower in the T2D subjects (31%) compared with the NGT subjects (35%) and showed significant protection against diabetes (odds ratio 0.85, 95% confidence interval 0.75-0.97, P=0.019). Regression analysis according to a recessive model taking the CC+CT genotype as the reference showed that the TT genotype was protective against diabetes (odds ratio 0.71, 95% confidence interval 0.50-0.99, P=0.048). Adjusting this P value by the number of competing models (three) using Bonferroni's correction, we found that the association finding did not remain significant.
  
  
  CONCLUSIONS
  The "T" allele of the His1085His polymorphism in the INSR gene shows significant protection against diabetes. This study gains importance because there are no data available to date on the role of INSR variants in T2D in the Indian population.
authors: Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, 4 Conran Smith Road, Gopalapuram, Chennai, India.
authors: Dhanasekaran
authors: D
authors: Bodhini
authors: Mohanram
authors: M
authors: Sandhiya
authors: Saurabh
authors: S
authors: Ghosh
authors: Partha P
authors: PP
authors: Majumder
authors: M R Satyanarayana
authors: MR
authors: Rao
authors: Viswanathan
authors: V
authors: Mohan
authors: Venkatesan
authors: V
authors: Radha
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011972:Receptor, Insulin / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C435941:INSR protein, human; D011972:Receptor, Insulin