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


Abel López-Bermejo, Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Av. de Francia, s/n, 17007 Girona, Spain. Tel.: + 34 972 940200, ext. 2580; Fax: + 34 972 940270; E-mail:


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.

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

Patients 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).

Measurements 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.

Conclusion 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.