Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. SUBJECTS AND METHODS: 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). RESULTS: All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. CONCLUSION: The studied polymorphisms were not associated with GDM in a Brazilian population.

Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population

ABSTRACT Objective Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. Subjects and methods 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). Results All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively. Conclusion The studied polymorphisms were not associated with GDM in a Brazilian population.

The GCKR Gene Polymorphism rs780094 is a Risk Factor for Gestational Diabetes in a Brazilian Population.

BACKGROUND: The glucokinase regulatory protein (GCKR) regulates the activity of the glucokinase (GCK), which plays a key role in glucose homeostasis. Genetic variants in GCK have been associated with diabetes and gestational diabetes (GDM). Due to the relationship between GCKRP and GCK, polymorphisms in GCKR are also candidates for genetic association with GDM. The aim of this study was to evaluate the association between the GCKR rs780094 polymorphism and GDM in a Brazilian population. METHODS: 252 unrelated Euro-Brazilian pregnant women were classified as control (healthy pregnant women, n = 125) and GDM (pregnant women with GDM, n = 127) age-matched groups. Clinical and anthropometric data were obtained from all subjects. The GCKR rs780094 polymorphism was genotyped using fluorescent probes (TaqMan® , code C_2862873_10). RESULTS: Both groups were in Hardy-Weinberg equilibrium. The GCKR rs780094 polymorphism was associated with GDM in codominant and dominant models (P = 0.022 and P = 0.010, respectively). The minor allele (T) frequency for the control group in the study was 38.4% (95% CI: 32-44%), similar to frequencies reported for other Caucasian populations. CONCLUSION: Carriers of the C allele of rs780094 were 1.41 (odds ratio, 95% CI, 0.97-2.03) times more likely to develop GDM.

Perfil clínico-laboratorial e comprometimento vascular em pacientes com diabetes mellitus tipo 2 / Clinical and laboratory profile of type 2 diabetes and its vascular complications

O Diabetes mellitus (DM) é uma síndrome multifatorial cujas complicações matam 5% da população mundial todo o ano. A hiperglicemia crônica característica do DM promove disfunção endotelial e o desenvolvimento de complicações microvasculares, como nefropatia, retinopatia e neuropatia, e macrovasculares como o acidente vascular cerebral e infarto agudo do miocárdio (IAM). O DM é uma patologia com altas taxas de morbidade e mortalidade, o que torna relevante a realização de estudos epidemiológicos para investigar suas características. O objetivo deste trabalho foi analisar o perfil clínico-laboratorial e a presença de complicações vasculares em pacientes com DM tipo 2 (DM2). Foram selecionados 300 pacientes com DM2 atendidos no Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná (HC-UFPR). Dados clínico-laboratoriais foram coletados e analisados a partir do prontuário médico e do banco de dados do laboratório de análises clínicas do HC-UFPR. O projeto foi aprovado pelo Comitê de Ética em Pesquisa do Setor de Ciências da Saúde da UFPR (número CAAE: 01038112.0.0000.0102). Os participantes tinham média de idade de 62 anos, eram na maioria mulheres (73%), apresentavam obesidade, hipertensão e dislipidemia. Concentrações de hemoglobina glicada >7%, indicando mal controle glicêmico, foram detectadas em 60,3% dos pacientes com DM2 neste estudo. E 40,7% dos participantes apresentaram ao menos uma complicação vascular. Os dados encontrados reforçam as estatísticas que pacientes com DM2 apresentam hipertensão, dislipidemias e obesidade, e estão em maior risco para complicações vasculares que podem causar morbidade e mortalidade.

Diabetes mellitus (DM) is a multifactorial syndrome with complications that kill 5% of the global population per year. Chronic hyperglycemia promotes endothelial dysfunction and the development of microvascular complications such as nephropathy, retinopathy and neuropathy, as well as macrovascular complications, such as stroke and acute myocardial infarction (AMI). DM is a disease with high morbidity and mortality, which makes it relevant to conduct epidemiological studies to investigate its features. The aim of this study was to evaluate clinical and laboratory profile and the presence of vascular complications in patients with type 2 DM (DM2). A total of 300 patients with DM2 treated at the Endocrinology and Metabolism Service at the Clinical Hospital of Federal University of Parana (HC-UFPR) were selected. Clinical and laboratory data were collected and analyzed from the medical records and laboratory database of HC-UFPR. This study was approved by the Research Ethics Committee of the UFPR Health Sciences Sector (CAAE number: 01038112.0.0000.0102). The mean age of participants was 62 years, with mostly women (73%) presenting obesity, high blood pressure and dyslipidemia. Glycated hemoglobin concentrations >7%, indicating poor glycemic control, was detected in 60.3% of DM2 patients in this study, with 40.7% participants presenting at least one vascular complication. These results confirm the fact that DM2 patients have hypertension, dyslipidemia and obesity, and are at increased risk for vascular complications associated with high morbidity and mortality.

A proteína p16 é uma novo marcador para progressão neoplásica no colo uterino? / Is the protein p16 a new mark for neoplastic progression in the cervix?

A pesquisa para Papilomavírus humano (HPV) de alto risco é um importante instrumento no rastreamento do carcinoma cervical, juntamente com a citologia cérvico-vaginal. No entanto, existe uma necessidade de validação de marcadores moleculares para aumentar a especificidade desses testes para detecção de lesões intraepiteliais que podem progredir. A proteína p16 atua como supressora de tumor por bloquear as CDK4 e CDK6 mediadas pela fosforilação da pRb, resultando na inibição da transcrição E2F dependente e, consequente inibição da progressão do ciclo celular. Pesquisas utilizando teste imunohistoquímico para p16 tem mostrado sua positividade em praticamente 100% dos casos de HSIL, carcinomas escamosos e adenocarcinomas in situ, além de auxiliar nos nos casos de LSIL associados com HPV de alto risco, onde poderá estar sobre-expressa. A análise imunocitoquímica p16 pode também ser uma ferramenta útil nos casos em que a citologia é incapaz de distinguir HSIL de alterações inflamatórias, reativas ou mesmo de epitélio normal. A p16 pode ser um marcador molecular útil em casos de histologia e/ou citologia inconclusivos, estratificando pacientes de alto risco.