title: The tumour necrosis factor (TNF)-alpha-308GA promoter polymorphism is related to prenatal growth and postnatal insulin resistance.
abstract: OBJECTIVE
  Variation in the tumour necrosis factor gene, (TNF) has been associated with insulin resistance traits. We questioned whether the TNF-308G/A polymorphism is associated with birthweight and insulin resistance in children born small for gestational age (SGA), a patient population known to be at risk for insulin resistance.
  
  
  METHODS
  A cross-sectional, hospital-based study assessing insulin sensitivity in SGA children.
  
  
  METHODS
  One hundred and ninety-eight school-age children born either SGA (n=90, age 7.4+/- 4.5 years) or appropriate for gestational age (AGA, n=108, age 8.7+/- 4.0 years).
  
  
  METHODS
  All children were genotyped for the TNF-308G/A polymorphism; a biochemical profile was also performed in prepubertal SGA (n=58) and AGA (n=57) subjects.
  
  
  RESULTS
  Genotype frequencies for the TNF-308G/A single nucleotide polymorphisms (SNPs) (GG and GA/AA) differed between SGA and AGA children (86%vs. 72% and 14%vs. 28%, respectively; P=0.025). The GG genotype was associated with lower birthweight and birth length (2747.0+/- 23.3 g vs. 2851.0+/- 45.7 g, P=0.045, and 47.0+/- 0.2 cm vs. 48.2+/- 0.4 cm, P=0.011, respectively) and, in AGA but not in SGA children, with higher systolic blood pressure [103.3 (95% confidence interval (CI) 96.4-110.2) mmHg vs. 92.8 (84.9-100.7) mmHg; P=0.028], higher blood glucose [4.8 (4.7-5.0) mmol/l vs. 4.5 (4.3-4.8) mmol/l; P=0.042] and higher homeostasis model assessment for insulin resistance (HOMA-IR) index [1.4 (1.1-1.7) vs. 0.9 (0.4-1.3); P=0.005]. In multivariate analysis, the TNF-308GG genotype was an independent predictor of HOMA-IR during childhood, explaining 8% of its variance.
  
  
  CONCLUSIONS
  SGA children show increased frequency of the TNF-308G allele, an allele that is associated with prenatal growth and with postnatal insulin resistance. The TNF-308G/A polymorphism may have implications in the growth and metabolic abnormalities that characterise SGA children.
authors.affiliation: Paediatric Endocrinology, Sant Joan de Déu Children's Hospital, Barcelona, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Casano-Sancho
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
authors.forename: Eugènia
authors.initials: E
authors.lastname: Monrós
authors.forename: Carme
authors.initials: C
authors.lastname: Valls
authors.forename: Francesc-Xavier
authors.initials: FX
authors.lastname: Rodríguez-González
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
mesh_terms: D001724:Birth Weight / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000235:genetics; D049628:Body Size / Q000502:physiology; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha