The tumour necrosis factor (TNF)-alpha-308GA promoter polymorphism is related to prenatal growth and postnatal insulin resistance

• Published in: Clinical endocrinology (Oxford) 2006-02, Vol.64 (2), p.129-135
• Main Authors: Casano-Sancho, Paula, López-Bermejo, Abel, Fernández-Real, José Manuel, Monrós, Eugènia, Valls, Carme, Rodríguez-González, Francesc-Xavier, Ricart, Wifredo, Ibáñez, Lourdes
• Format: Article
• Language: English
• Subjects: Birth Weight - genetics; Blood Glucose - analysis; Blood Pressure - genetics; Body Size - physiology; Child; Cross-Sectional Studies; Female; Fetal Development - genetics; Gene Frequency - genetics; Genotype; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin - blood; Insulin Resistance - genetics; Male; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics; Receptors, Tumor Necrosis Factor, Type II - blood; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0300-0664
• DOI: 10.1111/j.1365-2265.2006.02434.x

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. A cross-sectional, hospital-based study assessing insulin sensitivity in SGA children. 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). 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. 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. 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.