RESUMO
OBJECTIVE: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth. PATIENTS AND METHODS: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients. RESULTS: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables. CONCLUSION: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional , Fator de Crescimento Insulin-Like I/genética , Insulina/genética , Polimorfismo Genético , Sequências de Repetição em Tandem/genética , Adenosina , Peso ao Nascer/genética , Glicemia/genética , Estatura/genética , Peso Corporal/genética , Brasil , Citosina , Feminino , Humanos , Recém-Nascido , Resistência à Insulina/genética , Fator de Crescimento Insulin-Like I/análise , Masculino , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth. PATIENTS AND METHODS: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients. RESULTS: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables. CONCLUSION: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance. .
Assuntos
Feminino , Humanos , Recém-Nascido , Masculino , Recém-Nascido Pequeno para a Idade Gestacional , Fator de Crescimento Insulin-Like I/genética , Insulina/genética , Polimorfismo Genético , Sequências de Repetição em Tandem/genética , Adenosina , Brasil , Peso ao Nascer/genética , Glicemia/genética , Estatura/genética , Peso Corporal/genética , Citosina , Resistência à Insulina/genética , Fator de Crescimento Insulin-Like I/análise , Fatores de RiscoRESUMO
BACKGROUND: Few children born small for gestational age (SGA) with IGF1 mutations have been reported. One of these patients presented a mutation at 3' untranslated region (UTR) at exon 6, probably affecting the polyadenylation process. OBJECTIVE: The objective of the study was to sequence the IGF1 gene of children born SGA. PATIENTS AND METHODS: IGF1 (exons 1-6) was directly sequenced in 53 SGA children without catch-up growth. Allelic variant frequency of the identified IGF1 polymorphisms was assessed in a total of 145 SGA children and in 180 controls born with adequate weight and length and adult height sd score greater than -2. RESULTS: No mutations were identified in the IGF1 coding regions in SGA children. In contrast, six allelic variants were identified in the upstream core polyadenylation signal located in IGF1 3' UTR at exon 6. The frequency of the different allelic variants was similar in SGA children and controls. It is noteworthy that the same allelic variant, previously described as causing severe IGF1 deficiency, was also observed in homozygous (n = 4) and heterozygous state (n = 6) in normal height controls, corresponding to 4% of studied alleles. The three most frequently identified allelic variants of IGF1 3' UTR showed no effect on height sd score of adult controls as well as on birth characteristics in SGA children. CONCLUSION: The polymorphisms identified in the upstream core polyadenylation signal at IGF1 exon 6 do not cause IGF1 deficiency as well as pre- and postnatal growth impairment, in contrast to previously reported data.
