RYGB and SG procedures demonstrated a similar impact on adipokine levels in women 1 year post-surgery. Both techniques may improve the course of chronic diseases and the state of inflammation associated with obesity.

Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and ε2/ε3/ε4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (ε2, ε3 and ε4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of ε2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/ 107 (6.5%); P < 0.05]. Therefore, our results suggest that the ε2 allele/ APOE might be a risk factor for diabetes in the Brazilian population.

Late-onset Alzheimer's disease (LOAD) is a multifactorial neurodegenerative disorder that corresponds to most Alzheimer's disease (AD) cases. Inflammation is frequently related to AD, whereas microglial cells are the major phagocytes in the brain and mediate the removal of Aβ peptides. Microglial cell dsyregulation might contribute to the formation of amyloid plaques, a hallmark of AD. Genome-wide association studies have reported genetic loci associated with the inflammatory pathway involved in AD. Among them, rs3865444 CD33, rs3764650 ABCA7, rs6656401 CR1, and rs610932 MS4A6A variants in microglial genes are associated with LOAD. These variants are proposed to participate in the clearance of Aβ peptides. However, their association with LOAD was not validated in all case-control studies. Thus, the present work aimed to assess the involvement of CD33 (rs3865444), ABCA7 (rs3764650), CR1 (rs6656401), and MS4A6A (rs610932) with LOAD in a sample from southeastern Brazil. The genotype frequencies were assessed in 79 AD patients and 145 healthy elders matched for sex and age. We found that rs3865444 CD33 acts as a protective factor against LOAD. These results support a role for the inflammatory pathway in LOAD.

Collagen XVIII, a proteoglycan, is a component of basement membranes (BMs). There are three distinct isoforms that differ only by their N-terminal, but with a specific pattern of tissue and developmental expression. Cleavage of its C-terminal produces endostatin, an inhibitor of angiogenesis. In its N-terminal, there is a frizzled motif which seems to be involved in Wnt signaling. Mutations in this gene cause Knobloch syndrome (KS), an autosomal recessive disorder characterized by vitreoretinal and macular degeneration and occipital encephalocele. This review discusses the effect of both rare and polymorphic alleles in the human phenotype, showing that deficiency of one of the collagen XVIII isoforms is sufficient to cause KS and that null alleles causing deficiency of all collagen XVIII isoforms are associated with a more severe ocular defect. This review besides illustrating the functional importance of collagen XVIII in eye development and its structure maintenance throughout life, it also shows its role in other tissues and organs, such as nervous system and kidney.

OBJECTIVE -The purpose of this study was to evaluate the effect of the single nucleotide polymorphism (SNP) Ϫ634GϾC at the 5Ј regulatory region of the vascular endothelial growth factor (VEGF) in the risk of proliferative diabetic retinopathy (PDR) in the Brazilian population of European ancestry with type 2 diabetes. RESEARCH DESIGN AND METHODS-A case-control study was conducted in 501 type 2 diabetic patients of European ancestry. Patients underwent a standardized clinical, ophthalmological, and laboratory evaluation. Of these, 167 patients had PDR (case patients), and 334 were considered as control subjects (patients without PDR) for PDR. A reference population (110 individuals of European ancestry) was also evaluated.RESULTS -No evidence of association between Ϫ634GϾC/VEGF and the presence of diabetic retinopathy or type 2 diabetes was observed (P Ͼ 0.05). However, CC homozygous for the SNP Ϫ634GϾC was significantly more frequent in patients with PDR (37 of 167; 22.2%) than in the corresponding control group (40 of 334; 12%) in accordance with a recessive model (P ϭ 0.003). This effect was further observed when creatinine, BMI, sex, duration of type 2 diabetes, HDL cholesterol, and systolic blood pressure were taken into account (odds ratio 1.9 [95% CI 1.01-3.79], P ϭ 0.04).CONCLUSIONS -The presence of the allele Ϫ634C/VEGF in homozygosity is an independent risk factor for the development of PDR in type 2 diabetic patients of European ancestry. Diabetes Care 30:275-279, 2007D iabetic retinopathy is a common microvascular complication in patients with diabetes, constituting a major cause of blindness in this group. Although the risk of development of this complication increases with poor glycemic control, there are several indications suggesting that the occurrence or progression of diabetic retinopathy also depends on genetic factors (1-3).Proliferative diabetic retinopathy (PDR), characterized by increased vascular permeability, tissue ischemia, and neovascularization, affects 10 -20% of diabetic patients (4). This process depends on the local production of angiogenic factors and components of the extracellular matrix, which will be substrates for endothelial migration. Vascular endothelial growth factor (VEGF), a potent activator of angiogenesis, enhances collateral vessel formation and increases the permeability of the microvasculature (5,6). VEGF expression is induced by high glucose levels and hypoxia and plays an important role in normal and abnormal angiogenesis (7-9). Its levels have been found to be markedly increased in the vitreous and aqueous fluids in the eyes of patients with PDR (10 -12).Several polymorphisms at the VEGF 5Ј regulatory region have been characterized and evaluated as risk alleles for the susceptibility or progression of both diabetic retinopathy and diabetic nephropathy through case-control studies (13-16). The single nucleotide polymorphism (SNP) Ϫ634GϾC was found to be associated with nonproliferative diabetic retinopathy (NPDR) and diabetic macular edema in type 2 diabetic pa...

Collagen XVIII can generate two fragments, NC11-728 containing a frizzled motif which possibly acts in Wnt signaling and Endostatin, which is cleaved from the NC1 and is a potent inhibitor of angiogenesis. Collagen XVIII and Wnt signaling have recently been associated with adipogenic differentiation and obesity in some animal models, but not in humans. In the present report, we have shown that COL18A1 expression increases during human adipogenic differentiation. We also tested if polymorphisms in the Frizzled (c.1136C>T; Thr379Met) and Endostatin (c.4349G>A; Asp1437Asn) regions contribute towards susceptibility to obesity in patients with type 2 diabetes (113 obese, BMI > or =30; 232 non-obese, BMI < 30) of European ancestry. No evidence of association was observed between the allele c.4349G>A and obesity, but we observed a significantly higher frequency of homozygotes c.1136TT in obese (19.5%) than in non-obese individuals (10.9%) [P = 0.02; OR = 2.0 (95%CI: 1.07-3.73)], suggesting that the allele c.1136T is associated to obesity in a recessive model. This genotype, after controlling for cholesterol, LDL cholesterol, and triglycerides, was independently associated with obesity (P = 0.048), and increases the chance of obesity in 2.8 times. Therefore, our data suggest the involvement of collagen XVIII in human adipogenesis and susceptibility to obesity.

Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault.

Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, prognosis, and risk prediction, enabling personalized treatments, improving therapy, and preventing overtreatment, undertreatment, and incorrect treatment. Several breast cancer biomarkers have been identified and, along with traditional biomarkers, they can assist physicians throughout treatment plan and increase therapy success. Despite the need of more data to improve specificity and determine the real clinical utility of some biomarkers, others are already established and can be used as a guide to make treatment decisions. In this review, we summarize the available traditional, novel, and potential biomarkers while also including gene expression profiles, breast cancer single-cell and polyploid giant cancer cells. We hope to help physicians understand tumor specific characteristics and support decision-making in patient-personalized clinical management, consequently improving treatment outcome.