title: Tumor necrosis factor-alpha--308 G/A polymorphism in obese Caucasians.
abstract: OBJECTIVE
  Tumor necrosis factor-alpha (TNF-alpha) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5'-flanking region of the TNF-alpha gene (G-308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and influences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population.
  
  
  METHODS
  We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Ernährung Geschwister)- Study for the TNF-alpha-G-308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels.
  
  
  RESULTS
  The frequency of the -308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (GG, n=118; GA, n=53; AA, n=5). There was a significant difference in allele frequencies of the polymorphism by BMI quartiles (I,<27.3 kg/m2; II, 27.3-31.9 kg/m2; III, 31.9-36.5 kg/m2; IV,>36.5 kg/m2, in each quartile n=44) with -308A allele carriers having a higher BMI than G allele carriers (P=0.013). Despite previous smaller studies that have related insulin resistance to the G-308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that the G-308A polymophism of the TNF-alpha gene is associated with BMI. The G-308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Nephrology, Universitätsklinkum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Brand
authors.forename: U
authors.initials: U
authors.lastname: Schorr
authors.forename: I
authors.initials: I
authors.lastname: Kunz
authors.forename: E
authors.initials: E
authors.lastname: Kertmen
authors.forename: J
authors.initials: J
authors.lastname: Ringel
authors.forename: A
authors.initials: A
authors.lastname: Distler
authors.forename: A M
authors.initials: AM
authors.lastname: Sharma
mesh_terms: D000483:Alleles; D001823:Body Composition; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha