Identification and Association of Single Nucleotide Polymorphisms of the FTO Gene with Indicators of Overweight and Obesity in a Young Mexican Population.

(1) Background: obesity is a global public health problem; various factors have been associated with this disease, and genetic factors play a very important role. Previous studies in multiple populations have associated a gene with fat mass and obesity (FTO). Thus, the present work aims to identify and determine associations between genetic variants of FTO with indicators of overweight and obesity in the Mexican population. (2) Methods: a total of 638 subjects were evaluated to compile data on body mass index (BMI), the percentage of body fat (%BF), the waist circumference (WC), the serum levels of triglycerides (TG), and food consumption. A total of 175 genetic variants in the FTO gene were sampled by a microarray in the evaluated population, followed by association statistical analyses and comparisons of means. (3) Results: a total of 34 genetic variants were associated with any of the 6 indicators of overweight and obesity, but only 15 showed mean differences using the recessive model after the Bonferroni correction. The present study shows a wide evaluation of FTO genetic variants associated with a classic indicator of overweight and obesity, which highlights the importance of genetic analyses in the study of obesity.

Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity.

Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood; DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (p-value = 0.05). Although the sampled population did not have previously diagnosed diseases, the evaluation results showed that 33% were overweight or obese according to BMI and 64% had non-clinically elevated levels of body fat. From the 74 SNP markers analyzed from the five previously mentioned genes, 62 showed polymorphisms within the sampled population, and only 35 of these had significant associations with clinical variables. The risk associations (OR > 1) occurred between clinical markers with elevated values for waist circumference, waist−height index, BMI, body fat percentage, glucose levels, insulin levels, HOMA-IR, triglyceride levels, cholesterol levels, LDL-c, low HDL-c, carbohydrate intake, and protein intake and SNPs of the LEP, LEPR, PCSK1, and MC4R genes. On the other hand, the protective associations (OR < 1) were associated with markers including elevated values for insulin, HOMA-IR, cholesterol, c-LDL, energy intake > 2440 Kcal/day, and lipid intake and SNPs of the LEP and LEPR genes and POMC. The present study describes associations between SNPs in leptin pathway genes, revealing positive and negative interactions between reported SNPs and the clinical markers related to obesity in a sampled Mexican population. Hence, our results open the door for the further study of new genetic variants and their influence on obesity.

Histological Grade and Tumor Stage Are Correlated with Expression of Receptor Activator of Nuclear Factor Kappa b (Rank) in Epithelial Ovarian Cancers.

The receptor activator of nuclear factor kappa B (RANK) is becoming recognized as a master regulator of tumorigenesis, yet its role in gynecological cancers remains mostly unexplored. We investigated whether there is a gradation of RANK protein and mRNA expression in epithelial ovarian cancer (EOC) according to malignancy and tumor staging. Immunohistochemical expression of RANK was examined in a cohort of 135 (benign n = 29, borderline n= 23 and malignant n = 83) EOCs. Wild type and truncated RANK mRNA isoform quantification was performed in a cohort of 168 (benign n = 26, borderline n = 13 and malignant n = 129) EOCs. RANK protein and mRNA values were increased in malignant vs. benign or borderline conditions across serous, mucinous and endometrioid cancer subtypes. Additionally, a trend of increased RANK values with staging was observed for the mucinous and serous histotype. Thus, increased expression of RANK appears associated with the evolution of disease to the onset of malignancy in EOC. Moreover, in some EOC histotypes, RANK expression is additionally associated with clinicopathological markers of tumor aggressiveness, suggesting a role in further progression of tumor activity.

Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population.

The elongation of very long chain fatty acids (ELOVL) is a family of seven enzymes that have specific functions in the synthesis of fatty acids. Some have been shown to be related to insulin secretion (ELOVL2), and in the lipid profile (ELOVL6) and patients with various pathologies. The present work focused on the study of ELOVL polymorphs with clinical markers of non-communicable chronic diseases in the Mexican population. A sample of 1075 participants was obtained, who underwent clinical, biochemical, and nutritional evaluation, and a genetic evaluation of 91 genetic variants of ELOVL was considered (2-7). The results indicate a 33.16% prevalence of obesity by body mass index, 13.84% prevalence of insulin resistance by homeostatic model assessment (HOMA) index, 7.85% prevalence of high cholesterol, and 20.37% prevalence of hypercholesterolemia. The deprived alleles showed that there is no association between them and clinical disease risk markers, and the notable finding of the association studies is that the ELOVL2 variants are exclusive in men and ELVOL7 in women. There is also a strong association of ELOVL6 with various markers. The present study shows, for the first time, the association between the different ELOVLs and clinical markers of chronic non-communicable diseases.

Receptor Activator of Nuclear Factor Kappa B (RANK) and Clinicopathological Variables in Endometrial Cancer: A Study at Protein and Gene Level.

The system integrated by the receptor activator of nuclear factor kappa B (RANK) and its ligand, RANKL, modulates the role of hormones in the genesis and progression of breast tumors. We investigated whether the expression of RANK was related with clinicopathological features of primary endometrial tumors. Immunohistochemistry was used in an endometrial cancer tissue array containing samples from 36 tumors. The amount of RANK mRNA was examined in a tissue scan cDNA array containing cDNA from 40 tumors. Normal endometrium was examined for comparison. Immunohistochemical analyses showed that RANK expression was higher in malignant than in normal endometrium (p < 0.05). RANK expression was related to histological grade (Pearson correlation index = 0.484, p < 0.001), but not to tumor stage or to age of the women. The gene expression was similar in malignant and normal endometrium. The study of RANK isoforms confirmed that the overall relative abundance of the three clearly identified transcripts was similar in normal and pathological endometrium. RANK protein expression increased from normal to malignant endometrium, and the expression level was related with tumor grade but not with stage or the age of subjects in endometrial cancer. In contrast, similar comparisons showed no change in RANK gene expression.

Determination of peritoneal phosphate transport as a tool for controlling serum phosphorus.

BACKGROUND: Hyperphosphataemia (serum phosphorus ≥5.5mg/dl) is an independent mortality factor for the dialysis population. We compared phosphorus, creatinine and urea peritoneal transport to demonstrate differences and indicate the relevance of these parameters in the control of serum phosphorus. MATERIAL AND METHOD: We included 60 patients on peritoneal dialysis and determined the dialysate/plasma phosphorus (D/P P) and creatinine (D/P Cr) ratios, weekly creatinine clearance (CrCl) and phosphorus clearance (PCl), weekly Kt/V of urea, and peritoneal phosphorus excretion (PEx). RESULTS: D/P P was higher in patients with normal phosphataemia, compared with those who were hyperphosphataemic 0.61±0.13 versus 0.54±0.10 (p=.035). We observed an adequate correlation between D/P P and D/P Cr, r=0.90, p<.05, but poor concordance between both, with a lower limit of −0.17 (−0.24 to −0.09 95% CI) and an upper limit of 0.47 (0.39-0.54 95% CI) for D/P Cr with respect to D/P P. PCl had an adequate correlation with D/P P in patients with a Kt/V ≥1.7 (r=0.384, p=.04) and in anuric patients (r=0.392, p=.04), but not with D/P Cr. There was poor concordance of the CrCl with respect to PCl with a lower limit of −13.54l/week/1.73m2 BSA (−21.68 to −5.4 95% CI) and an upper limit of 58.98l/week/1.73m2 BSA (50.84-67.12 95% CI). Total PEx was related to PCl (r=0.643, p<.05), while it was not related to CrCl (r=0.222, p=.23). Using the CHAID method, we created a classification tree for phosphorus transport based on its D/P, obtaining 5 nodes (≤0.5, 0.51-0.55, 0.56-0.66, 0.67-0.76, >0.76), with statistically significant differences between nodes for serum phosphorus, total and peritoneal PCl and weekly Kt/V of urea. CONCLUSIONS: D/P P and PCl are not concordant with D/P Cr and CrCl respectively and therefore their determination is a clinical tool to control serum phosphorus levels.

Association between peritoneal protein excretion, peritonitis and D/P phosphate, in patients on peritoneal dialysis.

INTRODUCTION: There is a relationship between increased transfer of solutes (increased D/P creatinine) and decreased ultrafiltration, increased mortality and risk of technique failure in peritoneal dialysis patients. High rates of solute transport are associated with increased peritoneal protein excretion (PPE) and this has been associated with an increased risk of peritonitis. Our objective was to evaluate the possible association between the PPE, the number of episodes of peritonitis and the D/P phosphate. MATERIAL AND METHODS: A prospective longitudinal cohort study in PD patients. D/P phosphate, PPE, the number of episodes of peritonitis, as well as adequacy parameters and clinical and biochemical variables were measured. RESULTS: We included 60 patients on ambulatory peritoneal dialysis. We found a significant positive correlation (r=.369, P=.005) between the D/P phosphate and PPE, as well as between the PPE and the number of episodes of peritonitis (r=.65, p=.044). Finally, we found that the higher PPE and D/P phosphate, the lower serum albumin was (r=­0.50, p=.001 and r=­0.621, p=.000, respectively). CONCLUSIONS: PPE is significantly associated with the number of episodes of peritonitis and the D/P phosphate.