title: [TNF-alpha PC-1 gene polymorphisms and pre-diabetes quantitative features in the Polish population].
abstract: BACKGROUND
  Genetics and environmental factors play a role in the pathogenesis of the complex disease, type 2 diabetes mellitus. Two major pathophysiological defects coexist in this disease: impairment of insulin secretion by beta-cells and decreased insulin sensitivity in peripheral tissues. The aim of the study was to examine whether two polymorphisms: the -308 G/A substitution in the promoter region of TNF-alpha gene and the K121Q amino acid variant of the PC-1 gene; influence insulin resistance in individuals with positive family history of type 2 diabetes mellitus.
  
  
  METHODS
  Sixty individuals were included into this study: 28 women and 32 men, all of them with normal glucose tolerance. Insulin and glucose serum levels were were assessed during the OGTT on fasting and at 30 and 120 minutes. Secondary indices of insulin resistance were calculated based on these measurements. Genotyping of the both examined polymorphisms was performed using the restriction fragment length polymorphism method (RFLP).
  
  
  RESULTS
  Homozygous and heterozygous carriers of the A allele in position -308 of the TNF-alpha gene promoter showed higher plasma insulin levels at 120 min OGTT versus GG carriers (44.77 microliters/ml; SD 40.4 vs. 26.82; SD 19.9; p = 0.04) and a higher ratio of the 30 min increment in insulin to the 30 min increment in glucose (35.4; SD 21.5 vs. 22.6: SD 21.5; p = 0.03). In addition, homo- and heterozygous carriers of the Q allele at residue 121 of the PC-1 gene showed higher plasma glucose levels at 120 min OGTT compared to the KK subjects (5.38 mmol/l, SD 1.19 vs. 4.48, SD 1.11; p = 0.03).
  
  
  CONCLUSIONS
  Our study suggests that both examined polymorphisms: the -308 G/A in the promoter region of TNF-alpha and K121Q amino acid variant of the PC-1; influence the development of insulin resistance as a prediabetic quantitative trait in a Polish population.
authors.affiliation: Katedra i Klinika Chorób Metabolicznych Collegium Medicum Uniwersytetu Jagiellońskiego, 31-501 Kraków, ul. Kopernika 15.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wanic
authors.forename: Maciej
authors.initials: M
authors.lastname: Małecki
authors.forename: Tomasz
authors.initials: T
authors.lastname: Klupa
authors.forename: Przemysław
authors.initials: P
authors.lastname: Witek
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kozek
authors.forename: Jacek
authors.initials: J
authors.lastname: Sieradzki
mesh_terms: D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011236:Prediabetic State / Q000453:epidemiology* / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases
vernacular_title: Wybrane polimorfizmy w genach TNF-alpha i PC-1 a przedcukrzycowe cechy ilościowe w populacji polskiej.