Evaluación del polimorfismo Pro12Ala del gen PPARƴ en mujeres con diabetes mellitus gestacional / Evaluation of the Pro12Ala polymorphism of the PPARƴ gene in women with gestational diabetes mellitus

Resumen OBJETIVO: Determinar la frecuencia del alelo Ala en una muestra de mujeres mexicanas con diabetes mellitus gestacional y asociar su repercusión en la glucemia. MATERIALES Y MÉTODOS: Estudio ambispectivo, observacional, transversal y correlacional efectuado en una cohorte de pacientes con diabetes gestacional atendidas entre los meses de enero a junio del 2014 en el Hospital Militar de Especialidades de la Mujer y Neonatología de la Secretaría de la Defensa Nacional en la Ciudad de México. Se evaluó el polimorfismo mediante amplificación de un fragmento de ADN mediante la reacción en cadena de la polimerasa (PCR) y su secuenciación. RESULTADOS: Se estudiaron 81 pacientes; 3 de ellas con el alelo Ala, con concentraciones de glucosa menores y antecedente de más abortos en comparación con las mujeres sin el alelo Ala. CONCLUSIONES: La coexistencia del alelo Ala en mujeres embarazadas con diagnóstico de diabetes mellitus gestacional pudiera tener un efecto protector en contra de la hiperglucemia en el embarazo y el riesgo de aborto.

Abstract OBJECTIVE: To determine the frequency of peroxisomal proliferator-activated receptor gamma (PPARg) polymorphism of proline substituted with an alanine in amino acid 12 (Pro12Ala), in women with gestational diabetes mellitus and associate its impact with glycemia. MATERIALS AND METHODS: An ambispective, observational, cross-sectional and correlational study was carried out in a cohort of women with gestational diabetes that included 81 pregnant women treated at the Military Hospital for Women's Specialties and Neonatology of the Ministry of National Defense in the city from Mexico. Polymorphism was evaluated by amplification of a DNA fragment by PCR Polymerase Chain Reaction and its sequencing. RESULTS: The results indicated that 13.5% of the women carriers of the Ala allele also had lower blood glucose values and a history with a higher number of abortions compared to women without the Ala allele. CONCLUSIONS: The presence of the Ala allele in pregnant women with gestational diabetes mellitus could have a protective effect against hyperglycemia in pregnancy and a risk of abortion.

Diseño y validación de un ensayo de minisecuenciación múltiple para detectar polimorfismos asociados con Síndrome Metabólico / Design and validation of a multiple minisequencing assay to detect polymorphisms associated with Metabolic Syndrome

Resumen Introducción: Es importante identificar los polimorfismos de interés clínico en patologías complejas como el Síndrome Metabólico. Por esto, las metodologías para su evaluación deben estar diseñadas y validadas correctamente, esto permite optimizar recursos y tiempo en la genotipificación y detección correcta de los alelos presentes en los individuos. Objetivo: Diseñar y validar una PCR múltiple, seguida de detección por minisecuenciación, para la genotipificación de ocho polimorfismos de nucleótido simple ubicados en el gen del Receptor Beta 3-Adrenérgico (rs4994 y rs4998), gen de la Apolipoproteina A5 (rs3135506 y rs2075291), gen de la Adiponectina (rs1501299 y rs2241766) y gen del Receptor Activador de la Proliferación de los Peroxisomas tipo gamma (rs1801282 y rs1800571), asociados con el síndrome metabólico. Materiales y métodos: Se diseñaron 24 cebadores para la amplificación y detección de ocho polimorfismos de nucleótido sencillo ubicados en cuatro genes candidatos a estar asociados con el síndrome metabólico, usando el software Primer3®. Dieciséis fueron diseñados para amplificar los polimorfismos y ocho para detectarlos por minisecuenciación. Las estructuras secundarias entre los cebadores se verificaron con el software Autodimer. Los polimorfismos se amplificaron simultáneamente y los fragmentos amplificados se acoplaron a las sondas diseñadas para detectar por minisecuenciación el alelo presente, por medio de bases marcadas con fluorocromos. Finalmente, los alelos fueron detectados por electroforesis capilar en un analizador genético ABI 310 y se interpretaron con el software GeneMapper®. La validación del multiplex se realizó genotipando 20 muestras de individuos, cada uno de ellos autorizó este procedimiento por medio del consentimiento informado. Resultados: Se obtuvieron los perfiles genéticos de los 20 controles genotipados, a partir de la amplificación múltiple, seguida de minisecuenciación, diseñada y validada para detectar los ocho polimorfismos. Conclusión: Se diseñó y validó un ensayo para la detección simultánea de los polimorfismos, ubicados en cuatro genes asociados con el Síndrome metabólico. Los cuales pueden ser empleados como referencia para futuros estudios poblacionales.

Abstract Introduction: It is important to identify the polymorphisms of clinical interest in complex pathologies such as Metabolic Syndrome. Therefore, the methodologies for its evaluation must be designed and validated correctly, this permits optimization of resources and time in genotyping and correct detection of the alleles present in individuals. Objective: To design and validate a multiplex PCR, followed by detection by minisequencing, for the genotyping of eight single nucleotide polymorphisms located in the Beta 3-Adrenergic Receptor gene (rs4994 and rs4998), Apolipoprotein A5 gene (rs3135506 and rs2075291), Adiponectin gene (rs1501299 and rs2241766) and gamma-type Peroxisome Proliferation Activating Receptor gene (rs1801282 and rs1800571), associated with metabolic syndrome. Materials and methods: Twenty-four primers were designed for the amplification and detection of eight single nucleotide polymorphisms located in four candidate genes to be associated with the metabolic syndrome, using the Primer3® software. Sixteen were designed to amplify the polymorphisms and eight to detect them by minisequencing. The secondary structures between the primers were verified with Autodimer software. The polymorphisms were simultaneously amplified, and the amplified fragments were coupled to probes designed to minisequence the present allele using fluorochrome-labeled bases. Finally, the alleles were detected by capillary electrophoresis using an ABI 310 genetic analyzer and analyzed with the GeneMapper® software. The validation of the multiplex was performed by genotyping 20 individual samples, each of them authorized this procedure through informed consent. Results: The genetic profiles of the 20 genotyped controls were obtained, from multiple amplification, followed by minisequencing, designed and validated to detect the eight polymorphisms. Conclusion: An essay was designed and validated for the simultaneous detection of polymorphisms, located in four genes associated with metabolic syndrome, and can used as a reference for future population studies.

Peroxisome proliferator activated receptor γ involved in pathogenesis of polycystic ovary syndrome / 上海交通大学学报（医学版）

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is characterized by hyperandrogenism, rare ovulation or anovulation, and ovarian polycystic changes. Due to the heterogeneity of clinical manifestations, the pathogenesis of PCOS has not yet been fully elucidated, but genetic factors are considered to be the main pathogenesis of PCOS. Changes in epigenetic modifications such as DNA methylation and X-chromosome inactivation patterns may affect the expression of androgen receptor genes and insulin genes, thereby altering androgen activity, increasing androgen levels, and ultimately leading to PCOS. Peroxisome proliferator activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. Peroxisome proliferator activated receptor γ (PPARG) is the major expression subtype of the PPARs family in ovarian granulosa cells. PPARG plays an irreplaceable physiological function in reproduction and metabolism. It is involved in ovarian steroid metabolism, ovarian tissue remodeling, granulosa cell cycle regulation and insulin-glucose metabolism. Further research on the role of PPARG in the pathogenesis of PCOS can provide a theoretical basis for the prediction, diagnosis and treatment of long-term complications, which is reviewed by this article.

Incidental renal cell carcinoma with endometrial adenocarcinoma: A rare case report

Incidental detection of two primaries call for oncosurgeon’s own judgment to decide the best therapeutic approach as no guidelines exist for the rarity of condition. This is the rare case of incidental renal cell carcinoma in a patient of endometrial carcinoma. Renal cell carcinoma was detected on preoperative MRI in a patient who presented as postmenopausal bleeding and histology proven endometrial carcinoma. Final histology confirmed dual primaries with uterine primary being endometrioid adenocarcinoma, whereas renal primary was clear cell carcinoma stage II. Estrogen receptors (ER) have been identified in Hamster and Mouse kidneys as well as in renal cell carcinoma tissues. High plasma estrogen found in some patients of synchronous renal and endometrial cancer may partly explain the association of these two primaries, though not in all cases. Increased serum leptin levels and a common low penetrance susceptibility gene have been reported in both these cancers.

Swim training and the genetic expression of adipokines in monosodium glutamate-treated obese rats

Objective The aim of this study was to evaluate the genetic expression of adipokines in the adipocytes of monosodium glutamate (MSG)-treated obese rats submitted to physical activity.Materials and methods Obesity was induced by neonatal MSG administration. Exercised rats (MSG and control) were subjected to swim training for 30 min for 10 weeks, whereas their respective controls remained sedentary. Total RNA was obtained from sections of the mesenteric adipose tissue of the rats. mRNA levels of adiponectin (Adipoq), tumor necrosis factor alpha (Tnf), peroxisome proliferator-activated receptor alpha (Ppara), and peroxisome proliferator-activated receptor gamma (Pparg) adipokines were quantified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).Results In the exercise-trained control group, the expression of Adipoq increased compared to the sedentary control, which was not observed in the MSG-obese rats. Increased levels of Tnf in MSG-obese rats were not reversed by the swim training. The expression of Ppara was higher in sedentary MSG-obese rats compared to the sedentary control. Swimming increased this adipokine expression in the exercise-trained control rats compared to the sedentary ones. mRNA levels of Pparg were higher in the sedentary MSG-rats compared to the sedentary control; however, the exercise did not influenced its expression in the groups analyzed.Conclusions In conclusion, regular physical activity was not capable to correct the expression of proinflammatory adipokines in MSG-obese rat adipocytes.

Polymorphisms in LEPR, PPARG and APM1 genes: associations with energy intake and metabolic traits in young children / Polimorfismos nos genes LEPR, PPARG e APM1: associações com ingestão energética e parâmetros metabólicos em crianças em idade precoce

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) in five genes - leptin, leptin receptor (LEPR), adiponectin (APM1), peroxisome proliferator-activated receptor gamma (PPARG) and uncoupling protein 1 - with anthropometric, metabolic, and dietary parameters in a Southern Brazilian cohort of 325 children followed up from birth to 4 years old. MATERIALS AND METHODS: SNPs were analyzed using polymerase chain reaction-based procedures, and their association with phenotypes was evaluated by t-test, analysis of variance, and general linear models. RESULTS: LEPR223Arg allele (rs1137101) was associated with higher daily energy intake at 4 years of age (P = 0.002; Pcorrected = 0.024). PPARG 12Ala-carriers (rs1801282) presented higher glucose levels than Pro/Pro homozygotes (P = 0.007; Pcorrected = 0.042). CONCLUSIONS: Two of the six studied SNPs presented consistent associations, showing that it is already possible to detect the influences of genetic variants on susceptibility to overweight in 4-year-old children.

OBJETIVO: Avaliar a associação de polimorfismos de nucleotídeo único (SNPs) em cinco genes: leptina, receptor da leptina (LEPR), adiponectina (APM1), receptor ativado por proliferadores de peroxissomas gama (PPARG) e proteína desacopladora 1 com parâmetros antropométricos, metabólicos e dietéticos em uma coorte sul-brasileira composta por 325 crianças acompanhadas desde o nascimento até os 4 anos. MATERIAIS E MÉTODOS: Os SNPs foram analisados por meio da reação em cadeia da polimerase e sua associação com os fenótipos foi avaliada utilizando teste T, análise de variância e análise fatorial. RESULTADOS: O alelo LEPR223Arg (rs1137101) foi associado a uma maior ingestão energética diária aos 4 anos (P = 0,002; Pcorrigido = 0,024). Os portadores do alelo PPARG12Ala (rs1801282) apresentaram maior glicemia em relação aos homozigotos Pro/Pro (P = 0,007; Pcorrigido = 0,042). CONCLUSÕES: Dois dos seis SNPs estudados apresentaram associações consistentes, mostrando que aos 4 anos de idade já é possível detectar as influências de variantes genéticas sobre a suscetibilidade ao excesso de peso.

Efeito da pioglitazona sobre o remodelamento ósseo em diabetes tipo 2 / Pioglitazone effect on bone remodeling in type 2 diabetes

Alterações morfológicas no tecido ósseo têm sido descritas nos usuários de hipoglicemiantes orais da classe das tiazolidinedionas (TZDs). Hipotetiza-se que alguns genes relacionados com a osteogênese e osteoclastogênese podem ser influenciados pelo tratamento farmacológico, entretanto, o exato mecanismo ainda não está bem esclarecido. O objetivo do estudo foi avaliar o efeito da pioglitazona no remodelamento ósseo através de genes envolvidos na osteoclastogênese em indivíduos recentemente diagnosticados com DM2 e modelos animais, com a finalidade de identificar marcadores genéticos sensíveis de alterações ósseas. Foram convidados para participar do estudo 199 indivíduos (100 diabéticos e 99 normoglicêmicos), no ambulatório de dislipidemias do Instituto Dante Pazzanese de Cardiologia. Os indivíduos diabéticos foram tratados com pioglitazona (15, 30, 45, 45 mg/ dia/ via oral) por 16 semanas. Foram colhidas amostras de sangue, antes e após o tratamento para avaliações laboratoriais, extração de DNA genômico e de RNA total. Os polimorfismos e a expressão do mRNA nas células sanguíneas foram determinados pela PCR em tempo real através do sistema TaqMan®. Para o estudo em modelo animal após a indução da dieta hiperlipídica por 32 semanas, foram utilizados 12 camundongos machos da linhagem C57BL/J6, os quais foram divididos em três grupos: controle (n=4); diabéticos induzidos pela dieta hiperlipídica (DH, n=4) e diabéticos induzidos pela dieta hiperlipídica e tratados com pioglitazona 35mg/Kg/dia por 16 semanas (DHP, n=4). Para os grupos experimentais foram colhidos: amostras de sangue, para exames laboratoriais; fêmures, para a extração do RNA total; e tíbias, para determinação dos parâmetros histomorfométricos. Os pacientes DM2 apresentaram diminuição nas concentrações séricas de osteocalcina e na expressão de OPG e aumento na expressão de VDR em comparação ao grupo NG (p<0,05). A expressão de RANKL e IL6 foi maior entre as mulheres, enquanto que a expressão de PPARG foi maior entre os homens com DM2 em comparação ao grupo NG (p=0,032). Pacientes DM2 antes do tratamento apresentaram glicemia e expressão do mRNA de IL6 negativamente associados ao cálcio ionizado, enquanto que as transcrições de TNFA e VDR foram associadas positivamente e negativamente com bALP respectivamente (p<0,05). O tratamento com pioglitazona reduziu a glicemia de jejum, glicemia pós-prandial, insulina, HOMA-IR, triglicerídeos, VLDL-C, tALP e bALP e aumentou a HDL, tACP, TNF-α e a transcrição de OPG (p<0,05). A glicemia basal associou-se positivamente com o cálcio ionizado. A expressão basal de OPG foi associado negativamente com tALP, enquanto que a expressão basal de TNFA foi associada positivamente com tALP e negativamente com tACP. A expressão basal IL6 foi associada positivamente com tALP, enquanto que a expressão basal de VDR foi associada negativamente com osteocalcina e positivamente com bALP em resposta ao tratamento (p<0,05). O polimorfismo RANK rs1805034 foi associado com redução na transcrição do gene RANK nos indivíduos DM2 e com o remodelamento ósseo após o tratamento com pioglitazona (p<0,05). O polimorfismo RANKL rs9525641 foi associado com aumento da transcrição gênica de RANKL nos indivíduos NG e DM2 e melhora da resposta farmacológica nos indivíduos DM2 tratados com pioglitazona (p<0,05). O polimorfismo rs3102735 do gene OPG foi associado com aumento da formação óssea nos indivíduos DM2 antes e após o tratamento (p<0,05). O genótipo CG do polimorfismo OPG rs2073618 foi associado com alteração da transcrição de OPG no grupo DM2 pré e pós-tratamento (p<0,05). O polimorfismo PPARG rs1801282 foi associado com menor risco para o desenvolvimento de diabetes (p<0,05). O polimorfismo PPARG rs2972162 foi associado com melhora da resistência insulínica nos indivíduos DM2 tratados com pioglitazona (p=0,017). O polimorfismo ESRI rs9340799 foi associado com redução da formação óssea nos indivíduos DM2 (p=0,038). Nos camundongos, após a indução da dieta hiperlipídica por 32 semanas, observou-se aumento do peso, da glicemia, do colesterol total, da expressão do mRNA de RANK, RANKL, IL6 e TNFA em fêmures e aumento de Tb.Sp e diminuição de BV/TV em comparação ao grupo controle (p<0,05). O tratamento com pioglitazona diminuiu a expressão de TNFA (p=0,028). As medidas histomorfométricas não alteraram-se após o tratamento (p>0,05). Os resultados sugerem que o estado hiperglicêmico e o tratamento influenciam os marcadores bioquímicos e moleculares. Os polimorfismos dos genes RANK, RANKL, OPG e ESRI parecem estar envolvidos no remodelamento ósseo independentemente da hiperglicemia e do tratamento e os polimorfismos do gene PPARG parecem estar envolvidos com menor risco para desenvolver diabetes e com a melhora da resistência insulínica em resposta ao tratamento com pioglitazona

Morphological changes in bone tissue have been reported in users of oral hypoglycemic class of thiazolidinediones (TZDs). It is hypothesized that some genes related to osteogenesis and osteoclastogenesis may be influenced by pharmacological treatment, however, was not aware exact mechanism. The study aims was to evaluate pioglitazone effect on bone remodeling through genes involved in osteoclastogenesis in individuals newly diagnosed with DM2 and animal models, in order to identify sensibles genetics markers of bone alterations. Were invited to participate in study 199 patients (100 diabetics and 99 normoglycemic), in dyslipidemia ambulatory of Institute Dante Pazzanese of Cardiology. Diabetic subjects were treated with pioglitazone (15, 30, 45 or 45 mg /day/oral) for 16 weeks. Blood samples were collected before and after treatment for laboratory evaluations, extraction of genomic DNA and total RNA. Polymorphisms and mRNA expression in blood cells was determined by real time PCR using TaqMan® system. For study in animal model after 32 weeks of fat diet induction, was used 12 male mice C57BL/J6, which were divided into three groups: control (n=4); induced diabetic fat diet (DH, n=4) and induced diabetic fat diet and treated with pioglitazone 35mg/Kg/day for 16 weeks (DHP, n=4). For experimental groups were collected: blood samples for laboratory tests; femurs, for extraction of total RNA; and tibias, to determine histomorphometric parameters. DM2 patients showed decrease in serum osteocalcin and OPG expression and increased VDR expression compared to NG group (p<0.05). RANKL and IL6 expression were higher among women, whereas PPARG expression was higher among men with DM2 compared to NG group (p=0,032). DM2 patients before treatment showed blood glucose and IL6 mRNA expression negatively associated with ionized calcium, whereas TNFA and VDR transcription are positively and negatively associated with bALP respectively (p<0.05). Pioglitazone treatment reduced fasting glucose, postprandial glucose, insulin, HOMA-IR, triglycerides, VLDL-C, tALP and bALP and increased HDL, tACP, TNF-α and OPG transcription (p<0.05). Basal blood glucose was positively associated with ionized calcium. Basal OPG expression was negatively associated with tALP, whereas basal TNFA expression was positively associated with tALP and negatively with tACP. Basal IL6 expression was positively associated with tALP, whereas basal VDR expression was negatively associated with osteocalcin and positively with bALP in response to treatment (p<0.05). RANK rs1805034 polymorphism was associated with RANK gene transcription reduction in subjects with DM2 and bone remodeling after treatment with pioglitazone (p<0.05). RANKL rs9525641 polymorphism was associated with increased RANKL gene transcription in NG and DM2 subjects and pharmacological response improvement in DM2 subjects treated with pioglitazone (p<0.05). OPG rs3102735polymorphism was associated with increased bone formation in DM2 subjects before and after treatment (p<0.05). CG genotype of OPG rs2073618 polymorphism was associated with OPG transcription change in DM2 group before and after treatment (p<0.05). PPARG rs1801282 polymorphism was associated with lower risk for diabetes development (p<0.05). PPARG rs2972162 polymorphism was associated with insulin resistance improvement in DM2 subjects treated with pioglitazone (p=0,017). ESRI rs9340799 polymorphism was associated with reduced bone formation in DM2 subjects (p=0,038). In mice, after 32 weeks of fat diet induction, was observed increase weight, blood glucose, total cholesterol and RANK, RANKL, IL6 and TNFA mRNA expression in femurs and Tb.Sp increase and BV/TV decrease compared to control group (p<0.05). Treatment with pioglitazone decrease TNFA (p=0,028). Histomorphometrics measurements not change after treatment (p>0.05). Results suggest that hyperglycemic state and treatment influence biochemical and molecular markers. RANK, RANKL, OPG and ESRI polymorphisms seens to be involved in bone remodeling regardless of hyperglycemia and treatment and PPARG gene polymorphisms seens to be associated with lower risk for diabetes development and with insulin resistance improvement in response to treatment with pioglitazone

Efecto de los polimorfismos Gly972Arg del gen IRS1, SNP43 del gen CAPN10 y Pro12Ala del gen PPARG2 sobre la falla secundaria a sulfonilureas y metformina en pacientes con diabetes tipo 2 de Yucatán México / Effect of the Gly972Arg, SNP43 and Pro12Ala polymorphisms of the genes IRS1, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in Yucatán México

La diabetes tipo 2 (DT2) es elevada en Yucatán; 52% de los afectados presentan falla al tratamiento con sulfonilureas y metformina. Una posible explicación es por polimorfismos en los genes IRS1, CAPN10, PPARG2, involucrados en la disfunción de la célula b pancreática y respuesta baja a la acción de insulina. Se determinó la asociación de los polimorfismos Gly972Arg, SNP43 y Pro12Ala con el riesgo a la falla al tratamiento con sulfonilurea y metformina, en pacientes con DT2 de Yucatán, México. Se estudiaron ciento treinta y dos pacientes, clasificados con base al control de la hiperglucemia con sulfonilureas y metformina, en grupos de respondedores (HbA1c<8%) y no respondedores (HbA1c > 8%) al tratamiento. De cada sujeto, se obtuvieron datos demográficos, antropométricos, clínicos y metabólicos. Los polimorfismos se identificaron mediante el análisis del ADN por PCR/RFLP y PCR/OAL. Se calcularon las frecuencias genotípicas y alélicas y el equilibrio de Hardy-Weinberg. Se analizó estadísticamente con X² y regresión logística múltiple (Epi-Info 2000 y SPSS versión 12). Se observó diferencia significativa (p = 0,027) en el riesgo a la falla al tratamiento 4,69 veces mayor en sujetos obesos con genotipo AA SNP43, comparado con sujetos con genotipo GA: X² (OR= 4,69, IC: 1,15-20,59) y regresión logística múltiple, p= 0,048, (OR= 3,72, IC: 1,009-13,718). Se identificó interacción entre el genotipo AA y el IMC>27 (p=0,009). Los hallazgos sugieren que el polimorfismo SNP43 podría influir en la respuesta al tratamiento con sulfonilureas y metformina, con expresión dependiente de obesidad.

In Yucatán, 52% of patients with type 2 diabetes (DT2) present secondary failure to treatment associated with sulphonylurea and metformin. A possible explanation may be due to polymorphisms in the genes IRS1, CAPN10, PPARG2, which are involved in pancreatic b cell dysfunction and a poor response to the action of insulin. The association of the polymorphisms Gly972Arg, SNP43, and Pro12Ala, of the genes IRS1, CAPN10, PPARG2, with the risk of failure to sulphonylurea and metformin therapies was determinated in patients with DT2 in Yucatán, México. One hundred and thirty and two subjects with DT2 were classified in groups of responders (HbA1c< 8%) and non-responders (HbA1c> 8%) to the treatment, according to the control of hyperglucemia with sulphonylurea and metformin. Demographic, anthropometric and metabolic data were obtained from each subject. The polymorphisms were identified by means of DNA analysis by PCR/RFLP and PCR/OAL. Genotypic and allelic frequencies and the Hardy-Weinberg equilibrium were determined. Statistical analyses consisted of X² and multiple logistic regression tests (Epi-Info 2000 and SPSS version 12). Obese subjects carrying the genotype AA SNP43 showed 4.69 times more risk of failure to respond to treatment (p=0.027), when compared with subjects sharing GA genotype: X² (OR= 4.69, IC: 1.15-20.59) and multiple logistic regression, p= 0.048, (OR= 3.72, IC: 1.009-13.718). The interaction between genotype AA and the BMI> 27 showed also a significant difference (p=0.009). The findings suggest the fact that polymorphism SNP43 may influence the response to treatment with sulphonylurea and metformin, the expression being dependent on obesity.