title: Combined effects of genetic and environmental factors on insulin resistance associated with reduced fetal growth.
abstract: It has been suggested that the insulin resistance (IR) associated with reduced fetal growth results from interactions between genetic factors and an unfavorable fetal environment. In addition, the adipose tissue seems to play a key role in this association. We investigated whether polymorphisms in tumor necrosis factor (TNF)-alpha(G-308A), beta3 adrenoreceptor (ADRB3)(G+250C), and peroxisome proliferator-activated receptor (PPAR)-gamma2(Pro12Ala), key molecules of the adipose tissue, might affect the IR associated with reduced fetal growth. They were genotyped in 171 subjects who were born small for gestational age (SGA) and in 233 subjects who were born appropriate for gestational age (AGA) and underwent an oral glucose tolerance test (OGTT). The SGA group showed higher serum insulin concentrations than the AGA group at fasting (P = 0.03) and after stimulation (P = 0.0007), whereas no difference in serum glucose concentrations was observed. The frequencies of the alleles of these three polymorphisms were similar in both groups. In neither group did the polymorphisms affect glucose tolerance. In the SGA group, fasting insulin-to-glucose ratios were significantly higher in the TNF/-308A (P = 0.03), the PPAR/Ala12 (P = 0.01), and the ADRB3/+250G (P = 0.02) carriers than in the noncarriers. Results were comparable for fasting insulin concentration and insulin excursion under OGTT. No such amplification was observed in the AGA group. The effects of the PPAR/ProAla12 (P = 0.005) and the ADRB3/G+250G (P = 0.009) gene polymorphisms on IR indexes were significantly potentiated by BMI in the SGA group. In conclusion, our data exemplify the interaction between intrauterine environmental and genetic factors in the development of the IR associated with reduced fetal growth. They also point to the key role of adipose tissue in this association.
authors.affiliation: INSERM Unit 457, Hôpital R. Debré, 48 Boulevard Sérurier, 75019 Paris, France. djacquet@infobiogen.fr
authors.forename: Delphine
authors.initials: D
authors.lastname: Jaquet
authors.forename: David A
authors.initials: DA
authors.lastname: Trégouët
authors.forename: Thierry
authors.initials: T
authors.lastname: Godefroy
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Didi
authors.initials: D
authors.lastname: Chevenne
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Paul
authors.initials: P
authors.lastname: Czernichow
authors.forename: Claire
authors.initials: C
authors.lastname: Lévy-Marchal
mesh_terms: D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005215:Fasting / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000502:physiology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D011110:Polymorphism, Genetic / Q000502:physiology*; D011247:Pregnancy / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D022702:Receptors, Adrenergic, beta-3; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha