Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.

Leptin receptor gene polymorphisms are associated with adiposity and metabolic alterations in Brazilian individuals / Polimorfismos no gene do receptor de leptina são associados com adiposidade e alterações metabólicas em indivíduos brasileiros

OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.

OBJETIVO: O estudo teve por objetivo investigar a influência de polimorfismos nos genes da leptina (LEP) e do receptor de leptina (LEPR) na adiposidade e em marcadores metabólicos, como leptina, glicose e lipí­deos, em uma amostra de nossa população. SUJEITOS E MÉTODOS: Um grupo de 326 indivíduos com idade de 30 a 80 anos, 87 homens e 239 mulheres, 148 obesos e 178 não obesos, e de etnia branca foi selecionado aleatoriamente em dois hospitais clínicos da cidade de São Paulo, Brasil. Medidas antropométricas, índice de massa corporal (IMC) e gordura corporal foram avaliados. Amostras de sangue foram obtidas para extração de DNA e determinações de leptina, receptor de leptina solúvel, glicose e lipídeos. Os polimorfismos LEP -2548G>A e LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) e Lys656Asn (c.1968G>C) foram detectados por PCR-RFLP. RESULTADOS: Leptina e lipídeos séricos aumentados e LEPR Arg223Arg (genótipo GG) foram associados com maior risco de obesidade (p < 0,05), enquanto foi encontrado risco reduzido de obesidade, em portadores de LEPR Arg109Arg (genótipo GG) (OR: 0,38, 95%CI: 0,19-0,77, p = 0,007). A análise de regressão linear múltipla mostrou relação entre o alelo LEPR 223Arg e circunferência abdominal e leptinemia aumentadas (p < 0,05), enquanto o alelo LEPR 109Arg foi associado com aumento de colesterol total e triglicerídeos (p < 0,05). Os portadores do haplotipo 3 do LEPR (AGG: 109Lys/233Arg/656Lys) tiveram maior risco aumentado para obesidade (OR: 2.56, 95% CI: 1.19-5.49, p = 0,017). Além disso, esse haplótipo foi associado com IMC, circunferência abdominal e leptinemia aumentados (p < 0,05). CONCLUSÕES: Polimorfismos de LEPR são associados com obesidade, hiperleptinemia e perfil lipídico aterogênico sugerindo seu papel potencial para a resistência à leptina e risco cardiovascular.

Frecuencia de los polimorfismos CYP1A1*2A y deleción del gen GSTM1 en pacientes con carcinoma de células escamosas de laringe en relación al hábito tabáquico: estudio piloto en Chile / Frequency of CYP1A1*2A and GSTM1 gene polymorphisms in Chilean patients with squamous cell carcinoma of the larynx in relation to smoking habit: a pilot study

Introducción: Entre los factores de riesgo para cáncer laríngeo (CL) son relevantes el consumo de tabaco y alcohol. Estos xenobióticos son metabolizados por un grupo de enzimas, entre las cuales están CYP1A1 y GSTM1, cuyas variantes polimórficas se postulan como factores de riesgo para esta enfermedad. Objetivos: Describir la frecuencia de las variantes de los polimorfismos de CYP1A1 y GSTM1 en un grupo de pacientes diagnosticados con CL. Analizar la posible correlación entre las variantes genéticas de ambas enzimas y la presencia de CL. Evaluar la influencia del hábito tabáquico en el riesgo de aparición de cáncer escamoso de laringe en pacientes con genotipos de riesgo. Material y método: Se seleccionaron 35 pacientes con CL entre los años 2000 y 2010 en Servicio de Otorrinolaringología del HBLT y 124 controles reclutados en el Centro de Investigaciones Farmacológicas y Toxicológicas (IFT). A todos los individuos se les registraron datos demográficos y extrajo una muestra de sangre para analizar las variantes polimórficas de CYP1A1 y GSTM1, mediante PCR-RFLP. Resultados: De un total de 35pacientes 54,3% presentan el genotipo GSTM1 (-/-) y 17,1% el genotipo CYP1A1*2A C/C. En el grupo control (n =140) estas frecuencias fueron de 19,35°% y 10,48%o, respectivamente. Se observó una correlación entre GSTM1 y el CL, estratificado por el hábito tabáquico y alcohólico. No se encontraron relaciones estadísticamente significativas con el hábito alcohólico y/o tabáquico. No se observaron asociaciones entre la patología y la combinación de genotipos o entre genotipos y el hábito tabáquico o alcohólico. Conclusiones: Los resultados muestran una asociación estadísticamente significativa entre la deleción de GSTM1 (-/-) y el riesgo de presentar CL, lo que refleja el importante papel que juega esta enzima en la desintoxicación de compuestos cancerígenos. Sin embargo, se requiere incrementar el número de pacientes para establecer apropiadamente la relación genético-ambiental que permite adjudicar un papel relevante a estos biomarcadores.

Introduction: Tobacco and alcohol consumption are recognized risk factors for squamous cell carcinoma of the larynx. These xenobiotics are metabolized by numerous enzymes, among which, CYP1A1 and GSTM1 gene polymorphisms have been identified as risk factors for developing tobacco related cancers as lung and laryngeal carcinomas. Nevertheless, these polymorphisms have not been studied in Chilean patients with squamous cell carcinoma of the larynx. Aim: To describe, for the first time, the frequency of CYP1A1 and GSTM1 gene polymorphisms in Chilean patients with squamous cell carcinoma of the larynx. Material and method: We conducted a case-control study. The case group consisted of 35 Chilean patients with squamous cell carcinoma of the larynx; the control group was formed by 124 Chilean subjects without cancer diagnosis. Demographic data as age, sex and quantification of tobacco smoking and alcohol consumption were recorded in all individuals. CYP1A1 and GSTM1 gene polymorphisms were evaluated by polymerase chain reaction and restriction enzymes (PCR-RFLP). Results: The frequency of CYP1A1*2A C/C genotype was 54, 3°% among laryngeal cancerpatients and 17,1%% among control subjects. The frequency ofGSTM1 (-/-) genotype was 19,35 %% among laryngeal cancer patients and 10,48%% among control subjects. There were no statistically significant relationships between this gene polymorphisms and tobacco smoking or alcohol consumption. There were no associations between the presence of both gene polymorphisms in the same individual and the presence of laryngeal cancer. Interestingly we found an OR of 8.69 (CI 2.90 to 26.01) for GSTM1 (-/-) polymorphism and laryngeal cancer, stratified by tobacco smoking and alcohol consumption. Conclusions: Our work shows that the deletion of GSTM1 could be an important risk factor for squamous cell carcinoma of the larynx in Chilean patients. This finding reflects the important role that detoxification of carcinogenic compounds plays in Chilean population. However, it is necessary to increase the number of studied patients to properly establish the genetic-environmental relationship ascribed to these biomarkers.