title: TLR4 gene polymorphisms: evidence for protection against type 2 diabetes but not for diabetes-associated ischaemic heart disease.
abstract: OBJECTIVE
  Several factors either predisposing or protecting from the onset of diabetes mellitus type 2 (DM2) have been proposed. Two specific polymorphisms of toll-like receptor 4 (TLR4; Asp299Gly and Thr399Ile) have recently been identified either as candidate protector genes against DM2 and associated neuropathy or risk alleles for the manifestation of diabetic retinopathy. The impact of these alleles on the risk for ischaemic heart disease (IHD) is controversial while their role in diabetes-associated IHD has never been studied.
  
  
  METHODS
  In order to clarify the potential impact of TLR4 polymorphisms on the predisposition for DM2 as well as on diabetes-related IHD vulnerability, the distribution of the mutant TLR4 Asp299Gly and Thr399Ile alleles in 286 DM2 patients and 413 non-DM2 controls with or without IHD, was examined.
  
  
  RESULTS
  Mutant alleles were predominantly detected in 79/413 non-diabetic individuals versus 15/286 DM2 patients (P<0.0001). The rates of positivity for mutant alleles were similar among diabetic patients with or without IHD (7/142 vs 8/144, P>0.1), whereas they proved different among non-diabetic individuals with or without IHD (39/145 vs 40/268, P=0.004). Following multivariate analysis, the difference between diabetic and non-diabetic subjects, with regard to TLR4 mutations alone, remained significant (P=0.04).
  
  
  CONCLUSIONS
  Mutant TLR4 alleles confer protection against DM2. However, their presence does not seem to play any role, protective or aggravating, in the manifestation of IHD either in diabetic or in non-diabetic individuals.
authors.affiliation: Departments of Gastroenterology Molecular Biology and Genetics, School of Medicine, University of Thessaly, 41110 Mezourlo, Larissa, Greece.
authors.forename: A C
authors.initials: AC
authors.lastname: Manolakis
authors.forename: A N
authors.initials: AN
authors.lastname: Kapsoritakis
authors.forename: E K
authors.initials: EK
authors.lastname: Tiaka
authors.forename: A
authors.initials: A
authors.lastname: Sidiropoulos
authors.forename: A
authors.initials: A
authors.lastname: Gerovassili
authors.forename: M
authors.initials: M
authors.lastname: Satra
authors.forename: D
authors.initials: D
authors.lastname: Vamvakopoulou
authors.forename: F
authors.initials: F
authors.lastname: Tsiopoulos
authors.forename: N
authors.initials: N
authors.lastname: Papanas
authors.forename: I
authors.initials: I
authors.lastname: Skoularigis
authors.forename: S P
authors.initials: SP
authors.lastname: Potamianos
authors.forename: N
authors.initials: N
authors.lastname: Vamvakopoulos
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D019610:Cytoprotection / Q000235:genetics; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4