title: Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced prevalence of diabetic neuropathy in patients with type 2 diabetes.
abstract: OBJECTIVE
  To establish whether single nucleotide polymorphisms (Asp299Gly and Thr399Ile) of the toll-like receptor 4 have an association with late diabetic complications.
  
  
  METHODS
  The study was conducted in 246 type 1 and 530 type 2 diabetic patients. The alleles of both polymorphisms were detected using PCR and subsequent cleavage by NcoI and HinfI restriction endonucleases.
  
  
  RESULTS
  No difference was found between type 1 and type 2 diabetic patients in the prevalence of alleles of the Asp299Gly and Thr399Ile polymorphisms. In most cases, the alleles Gly299 and Ile399 occurred in a co-segregatory manner. The prevalence of the Gly299/Ile399 haplotype was 10.6 and 12.1% in type 1 and type 2 diabetic patients, respectively (P = 0.63). No association with diabetic nephropathy or diabetic neuropathy was found in type 1 diabetic patients. In type 2 diabetic patients, however, heterozygote carriers of the Asp299Gly and Thr399Ile genotypes had a significantly reduced prevalence of diabetic neuropathy (odds ratio 0.35 [95% CI 0.19-0.61]; P = 0.0002); no association with diabetic nephropathy was found.
  
  
  CONCLUSIONS
  Our data indicate that Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of diabetic neuropathy in type 2, but not in type 1, diabetes. Thus different mechanisms may be involved in the pathophysiology of diabetic neuropathy in type 1 and type 2 diabetes.
authors.affiliation: Department Medicine I, University of Heidelberg, Heidelberg, Germany.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Rudofsky
authors.forename: Peter
authors.initials: P
authors.lastname: Reismann
authors.forename: Steffen
authors.initials: S
authors.lastname: Witte
authors.forename: Per M
authors.initials: PM
authors.lastname: Humpert
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
authors.forename: Jörg
authors.initials: J
authors.lastname: Tafel
authors.forename: Valery V
authors.initials: VV
authors.lastname: Nosikov
authors.forename: Andreas
authors.initials: A
authors.lastname: Hamann
authors.forename: Peter
authors.initials: P
authors.lastname: Nawroth
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
mesh_terms: D019943:Amino Acid Substitution; D001224:Aspartic Acid; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003929:Diabetic Neuropathies / Q000453:epidemiology* / Q000235:genetics*; D005838:Genotype; D005998:Glycine; D006801:Humans; D007532:Isoleucine; D008562:Membrane Glycoproteins / Q000235:genetics*; D020125:Mutation, Missense; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011956:Receptors, Cell Surface / Q000235:genetics*; D013912:Threonine; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D044465:White People / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D007532:Isoleucine; D013912:Threonine; D001224:Aspartic Acid; D005998:Glycine