The tumour necrosis factor (TNF)-alpha-308GA promoter polymorphism is related to prenatal growth and postnatal insulin resistance.
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.
Casano-Sancho
Paula
P
Paediatric Endocrinology, Sant Joan de Déu Children's Hospital, Barcelona, Spain.
López-Bermejo
Abel
A
Fernández-Real
José Manuel
JM
Monrós
Eugènia
E
Valls
Carme
C
Rodríguez-González
Francesc-Xavier
FX
Ricart
Wifredo
W
Ibáñez
Lourdes
L
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*
D001786:Blood Glucose; D007328:Insulin; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha