RESUMO
BACKGROUND: High birth weight (HBW) is considered a key predictor of the development of chronic diseases, such as Type 2 Diabetes (T2D). Foetal growth depends on many factors, among which placental function is critical. Some genes with expression in the placenta, such as GRB10, are known to be involved in the regulation of insulin receptor pathways and the size of mouse littermates. AIM: To evaluate whether the intronic polymorphism rs12540874 A>G of the GRB10 gene is associated with HBW in term newborns. STUDY DESIGN: A total of 51 healthy term newborns were enrolled in a nested case-control study. The case group was defined by the presence of HBW (n=17) and the control group by newborns with normal birth weight (NBW n=34). Maternal and foetal factors influencing HBW were considered as exclusion criteria. The polymorphism was determined through real-time PCR using TaqMan technology. Categorical variables were evaluated with descriptive statistics, and multivariate logistic regression analysis was used to evaluate the association between polymorphism and HBW. RESULTS: The newborns in the case group had a longer gestation period (39. 7 ± 1.0 and 38.8 ± 1.8 weeks) and higher insulin levels at birth (9.5 ± 4.0 and 5.7 ± 3.4 µU/mL) than the newborns in the control group. The multivariate regression analysis, adjusted for weeks of gestation, showed a significant association between the SNP rs12540874 A>G of the GRB10 gene with HBW (OR 4.9; CI95% 1.10-22.10 p=0.02). CONCLUSIONS: Our results suggest that the SNP rs12540874 A>G, an intronic SNP of the gene GRB10, is associated with HBW.
Assuntos
Peso ao Nascer/genética , Doenças Fetais/genética , Proteína Adaptadora GRB10/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Hiperinsulinismo/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Humanos , Recém-Nascido , Insulina/metabolismo , Modelos Logísticos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genéticaRESUMO
BACKGROUND: The SLC38A4 gene is related to system 'A' activity, which seems to be related to impaired gluconeogenesis. The objective of this study was to determine whether the 292 C>T and 1304 G>A polymorphisms of SLC38A4 gene are associated with hyperglycaemia in humans. METHODS: A total of 227 individuals were enrolled in a case-control study, in which hyperglycaemia was defined by plasma glucose levels ≥95 mg/dL. Genotyping was carried out by using real-time polymerase chain reaction. RESULTS: The frequency of mutant alleles of SLC38A4 gene for single-nucleotide polymorphism (SNP) 1304 G>A was 23.6% and 30.2% for SNP 292 C>T. The frequency of allele T for the SNP 292 C>T in the case and control groups did not show significant differences, whereas the frequency of allele A for the SNP 1304 G>A was significantly higher in the case group than in the control group (p = 0.04). In the logistic regression analysis, the SNP 1304 G>A [odds ratio (OR) 1.78; 95%CI 1.04-3.05, p = 0.03] but not SNP 292 C>T (OR 1.41; 95%CI 0.80-2.47, p = 0.23) showed a significant association with hyperglycaemia. After adjusting by body mass index, waist circumference and triglycerides, the SNP 1304 G>A remained significantly associated with hyperglycaemia (OR 2.13; 95%CI 1.18-3.83, p = 0.03). Pair wise linkage disequilibrium showed correlation (D' > 0.82) between 292 C>T and 1304 G>A SNPs. Haplotype association with hyperglycaemia also showed significant association between both homozygous mutant alleles (A/T) and hyperglycaemia (OR 1.68; 95%CI 1.01-2.79, p = 0.048). CONCLUSIONS: Our results suggest that mutant allele A for SNP 1304 G>A of SLC38A4 gene is associated with hyperglycaemia.