Placental SLC38A4 gene polymorphisms 1304 G > A and 292 C > T, and their association with glucose > 95 mg/dL in normal weight full-term healthy newborns / Polimorfismos 1304 G > A y 292 C > T del gen placentario SLC38A4 y su asociación con glucosa > 95 mg/dL en recién nacidos a término, sanos y con peso normal al nacimiento

Abstract Background: The SLC38A4 gene encodes for the SNAT4 protein, which has been related to glucose metabolic alterations in human newborns. This study aimed to determine whether the 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene are associated with the presence of glucose levels > 95 mg/dL in normal weight full-term healthy newborns. Methods: We conducted a case–control study and analyzed 50 normal weight full-term healthy newborns. Groups were defined based on glucose levels: > 95 mg/dL (cases; n = 13) and < 95 mg/dL (controls; n = 37). The 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene were determined through quantitative polymerase chain reaction using placental DNA. The association between polymorphism and glucose levels > 95 mg/dL was established using multivariate logistic regression analysis. Results: No significant differences were observed either for gestational age or body weight at birth between groups. In the case group, newborns showed significantly higher homeostatic model assessment for insulin resistance than those in the control group (p < 0.0005). The odds ratio (OR) between the SLC38A4 gene 292 C > T single-nucleotide polymorphism (SNP) and glucose levels > 95 mg/dL was 7.78 (p = 0.024), whereas no significant association was found for the 1304 G > A SNP (OR 1.46; p = 0.77). Conclusions: Our results suggest that the SLC38A4 gene 292 C > T SNP is associated with glucose levels > 95 mg/dL in normal weight full-term healthy newborns.

Resumen Introducción: El gen SLC38A4 codifica la proteína SNAT4, que se ha relacionado con alteraciones en el metabolismo de la glucosa en los humanos. El objetivo de este estudio fue determinar si los polimorfismos 1304 G > A y 292 C > T del gen SLC38A4 se asocian con concentraciones de glucosa > 95 mg/dL en recién nacidos a término Métodos: Se llevó a cabo un estudio de casos y controles con 50 recién nacidos a término, sanos, con peso normal al nacimiento. Los grupos se definieron de acuerdo con las concentraciones de glucosa: > 95 mg/dL (casos; n = 13) y < 95 mg/dL (controles; n = 37). Los polimorfismos 1304 G > A y 292 C > T del gen SLC38A4 se genotipificaron por qPCR utilizando ADN de la placenta. La asociación entre los polimorfismos y la concentración de glucosa > 95 mg/dL se estableció mediante la estimación de la razón de momios (RM) en un análisis múltiple de regresión logística. Resultados: No se observaron diferencias estadísticamente significativas para la edad gestacional y el peso al nacer entre los grupos de estudio. El modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) fue significativamente más alto en los recién nacidos del grupo de casos que en el grupo control (p < 0.0005). La RM mostró asociación significativa entre el polimorfismo de nucleótido único (SNP) 292 C > T del gen SLC38A4 y la concentración de glucosa > 95 mg/dL (RM: 7.78; p = 0.024); el SNP 1304 G > A no mostró asociación significativa (RM: 1.46; p = 0.77). Conclusiones: Los resultados de este estudio sugieren que el SNP 292 C > T del gen SLC38A4 se asocia con concentraciones de glucosa > 95 mg/dL en recién nacidos a término.

Placental SLC38A4 gene polymorphisms 1304 G > A and 292 C > T, and their association with glucose > 95 mg/dl in normal weight full-term healthy newborns.

BACKGROUND: The SLC38A4 gene encodes for the SNAT4 protein, which has been related to glucose metabolic alterations in human newborns. This study aimed to determine whether the 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene are associated with the presence of glucose levels > 95 mg/dL in normal weight full-term healthy newborns. METHODS: We conducted a case-control study and analyzed 50 normal weight full-term healthy newborns. Groups were defined based on glucose levels: > 95 mg/dL (cases; n = 13) and < 95 mg/dL (controls; n = 37). The 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene were determined through quantitative polymerase chain reaction using placental DNA. The association between polymorphism and glucose levels > 95 mg/dL was established using multivariate logistic regression analysis. RESULTS: No significant differences were observed either for gestational age or body weight at birth between groups. In the case group, newborns showed significantly higher homeostatic model assessment for insulin resistance than those in the control group (p < 0.0005). The odds ratio (OR) between the SLC38A4 gene 292 C > T single-nucleotide polymorphism (SNP) and glucose levels > 95 mg/dL was 7.78 (p = 0.024), whereas no significant association was found for the 1304 G > A SNP (OR 1.46; p = 0.77). CONCLUSIONS: Our results suggest that the SLC38A4 gene 292 C > T SNP is associated with glucose levels > 95 mg/dL in normal weight full-term healthy newborns.

Association of the 5HTTLPR Polymorphism with Obesity in Mexican Women with High Native American Ancestry.

Aims: The 5HTT gene has been associated with obesity; this study aimed to determine the association between L- and S-alleles at the 5HTTLPR polymorphism with obesity in indigenous Mexican populations. Materials and Methods: A total of 362 individuals, 289 belonging to eight Native American (NA) groups; 40 Mexican mestizos; and 33 Caucasian Mennonites were enrolled in a cross-sectional study. High (≥90%) and low (<90%) NA ancestry was molecularly determined. A body mass index >30 kg/m2 was considered as obese. The L- and S-alleles of the 5HTTLPR locus were identified by PCR; the association between alleles and obesity was performed by logistic regression analysis. Results: A significantly lower prevalence of obesity (35%) was observed in participants from communities with high NA ancestry (p < 0.005). Under a dominant heritance model the L-allele was associated with obesity in women with high NA ancestry (odds ratio [OR] 7.27; 95% confidence interval [CI] 1.6-32.5; p = 0.009) but not in women with low NA ancestry (OR 0.83; 95% CI 0.3-2.2; p = 0.71); no association was observed in men. Conclusion: Our results suggest that the 5HTTLPR L-allele is a risk factor for developing obesity in Mexican women with high NA ancestry (≥90%).

Association of the intronic polymorphism rs12540874 A>G of the GRB10 gene with high birth weight.

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.

Association of the polymorphisms 292 C>T and 1304 G>A in the SLC38A4 gene with hyperglycaemia.

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.