Relationship between variants of the leptin gene and obesity and metabolic biomarkers in Brazilian individuals / Associação entre variantes do gene de leptina e obesidade e biomarcadores metabólicos em indivíduos brasileiros

OBJECTIVE: The relationship between variants of the leptin gene (LEP) and obesity and metabolic biomarkers was investigated in Brazilian individuals. SUBJECTS AND METHODS: One-hundred-ten obese (BMI > 30 kg/m²) and 100 non-obese individuals (145 women and 65 men, aged 49 ± 14 years) were randomly selected. Plasma leptin, glycemia, serum lipid measurements and LEP -2548G>A and 3'HVR polymorphisms were analyzed. RESULTS: The LEP -2548GG genotype was associated with a 2.2 percent and 2.0 percent increase in BMI (p = 0.009) and plasma leptin (p = 0.031), respectively. 3'HVR I/II (classes I/I+I/II) genotypes contributed with 1.8 percent of BMI values (p = 0.046). LEP I/G combined genotypes (I/IGG, I/IGA and I/IIGG) were associated with obesity, and increased BMI, waist circumference, leptin and triglycerides (p < 0.05). These relationships were found in women (p < 0.05) but not in men. LEP I/G combined genotypes were not associated with hypertension, hyperglycemia, dyslipidemia and coronary artery disease. CONCLUSIONS: LEP I/G combined genotypes are associated with obesity-related metabolic biomarkers and phenotype in a gender-dependent manner.

OBJETIVO: A relação entre as variantes do gene da leptina (LEP) e obesidade e biomarcadores metabólicos foi investigada em indivíduos brasileiros. SUJEITOS E MÉTOODS: Cento e dez indivíduos obesos (IMC > 30 kg/m²) e 100 não obesos (145 mulheres e 65 homens, idade 49 ± 14 anos) foram selecionados aleatoriamente. Leptina plasmática, glicemia, lípides séricos e polimorfismos LEP -2548G>A e 3'HVR foram analisados. RESULTADOS: O genótipo -2548GG foi associado com aumento de 2,2 por cento e 2,0 por cento no IMC (p = 0,009) e leptina plasmática (p = 0,031), respectivamente, enquanto os genótipos 3´HVR I/II (classes I/I+I/II) contribuíram com 1,8 por cento dos valores de IMC (p = 0,046). Os genótipos combinados LEP I/G (I/IGG, I/IGA e I/IIGG) foram associados com obesidade e IMC aumentado, circunferência abdominal, leptina e triglicérides aumentados (p < 0,05). Essas relações foram encontradas em mulheres (p < 0,05), mas não em homens. Os genótipos LEP I/G combinados não foram associados com hipertensão, hiperglicemia, dislipidemia e doença arterial coronariana. CONCLUSÕES: Genótipos combinados LEP I/G são associados com biomarcadores metabólicos e fenótipo de obesidade de forma gênero-dependente.

The Association of Leptin Gene -2548G/A Functional Polymorphism with Antipsychotic Agent-induced Type 2 Diabetes in Schizophrenic Patients / 中国心理卫生杂志

Objective: To investigate whether antipsychotic agent-induced type 2 diabetes was associated with leptin gene -2548G/A functional polymorphism in schizophrenia patients who had treated by antipsychotics chronically. Methods: Fasting plasma glucose, 2-hour post meal plasma glucose, fasting plasma leptin and fasting plasma insulin were measured in 110 patients with chronic schizophrenia whose natural courses of the disorder were more than 5 years. According to the level of plasma glucose, these patients were divided into three groups, diabetes mellitus group, abnormal regulating glucose group and normal glucose group. The polymorphisms in the leptin promoter region (-2548 G/A) were determined with PCR-RFLP in the patients. Results: The patients in DM group were more likely to be homozygous for the -2548AA genotype. As compared with the patients with -2548AG/GG combined genotype, the patients with -2548AA genotype had significant increase in the level of plasma leptin(P=0.019). Conclusion: The -2548G/A polymorphism in promoter region of leptin gene may be associated with type 2 diabetes in schizophrenic patients treated by antipsychotics chronically. -2548A allele of leptin gene may be a genetic risk factor for the development of type 2 diabetes during antipsychotic treatment.

The Relations between Bone Density and Plasma Leptin in Postmenopausal Women

OBJECTIVE: To investigate the relationship between the plasma leptin concentration and bone metabolism in postmenopausal women with osteoporosis to improve the understanding of the role of leptin in controlling bone mass. METHOD: Fifty four postmenopausal women (ages 64+/- 8.59 years, body weights 58.14+/- 6.92 kg) with osteoporosis were included. The biochemical markers of bone metabolism and serum leptin concentration were measured using the radioimmunoassay. Bone mineral densities were measured by dual energy X-ray absorptiometry. And we investigate the correlation between serum leptin concentration and the biochemical markers of bone metabolism or bone mineral density. RESULTS: The bone mineral densities were 0.639+/- 0.130 g/cm2 in mid-lumbar area, 0.684+/- 0.098 g/cm2 in femoral neck and 0.491+/- 0.117 g/cm2 in Ward's triangle. The mean value of serum osteocalcin was 26.84+/- 16.73 ng/ml, the mean value of urine deoxypyridinoline was 11.84+/- 6.08 nmol/mmol Cr, and the plasma concentration of leptin was 11.51+/- 8.64 ng/ml. There was no correlation between plasma leptin concentrations and the markers of bone metabolism or bone mineral density. CONCLUSION: We could not confirm the significant correlation between the circulating leptin concentration and the bone mass in postmenopausal women. Our data suggest circulating plasma leptin does not have a significant direct influence on bone metabolism and bone mass in postmenopausal women.