Medicine and Health Sciences Commons^™

Genetic Variants In Kcnj11, Tcf7l2 And Hnf4a Are Associated With Type 2 Diabetes, Bmi And Dyslipidemia In Families Of Northeastern Mexico: A Pilot Study, Hugo Leonid Gallardo-Blanco, Jesus Zacarias Villarreal-Perez, Ricardo Martin Cerda-Flores, Andres Figueroa

Computer Science Faculty Publications and Presentations

The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low‑density lipoprotein (LDL), very LDL (VLDL), high‑density lipoprotein (HDL) and triglycerides were evaluated. Three genetic markers previously associated with metabolic syndromes were identified in the sample population, including KCNJ11, TCF7L2 and HNF4A. The KCNJ11 …

Lack Of Interaction Between Erbb2 And Insulin Receptor Substrate Signaling In Breast Cancer, Sarah M. Farabaugh, Bonita T. Chan, Xiaojiang Cui, Robert Dearth, Adrian V. Lee

Biology Faculty Publications and Presentations

Background: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbBmediated anti-estrogen resistance in breast cancer. Herein, we examined crosstalk between ErbB2 and IRSs using cancer cell lines and transgenic mouse models.

Methods: MMTV-ErbB2 and MMTV-IRS2 transgenic mice were crossed to create hemizygous MMTV-ErbB2/MMTVIRS2 bigenic mice. Signaling crosstalk …

The Genetic Architecture Of Type 2 Diabetes, Christian Fuchsberger, Jason Flannick, Tanya M. Teslovich, Anubha Mahajan, Vineeta Agarwala, Kyle J. Gaulton, Joanne E. Curran, Satish Kumar, John Blangero, Ravi Duggirala

School of Medicine Publications and Presentations

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping …

Inferring Causal Molecular Networks: Empirical Assessment Through A Community-Based Effort, Steven M. Hill, Laura M. Heiser, Thomas Cokelaer, Michael Unger, Nicole K. Nesser, Daniel E. Carlin, Yang Zhang, Artem Sokolov, Evan O. Paull, Dong-Chul Kim

Computer Science Faculty Publications and Presentations

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology …

New Loci For Body Fat Percentage Reveal Link Between Adiposity And Cardiometabolic Disease Risk, Yingchang Lu, Felix R. Day, Stefan Gustafsson, Martin L. Buchkovich, Jianbo Na, Veronique Bataille, Diana L. Cousminer, Zari Dastani, Joanne E. Curran, John Blangero

School of Medicine Publications and Presentations

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed …

Metabolic Control In Patients With Type 2 Diabetes Mellitus In A Public Hospital In Peru: A Cross-Sectional Study In A Low-Middle Income Country, Irma Huayanay, Felix Guerra-Castañon, Maria Lazo-Porras, Ana Castaneda-Guarderas, Nimmy Josephine Thomas, Ana-Lucia Garcia-Guarniz, Augusto A. Valdivia Bustamante, German Malaga

School of Medicine Publications and Presentations

Objective

The objective of this study was to assess patients’ achievement of ADA (American Diabetes Association) guideline recommendations for glycosylated hemoglobin, lipid profile, and blood pressure in a type 2 diabetes mellitus (T2DM) outpatient clinic in a low-middle income country (LMIC) setting.

Methods

This is a descriptive cross-sectional study with 123 ambulatory T2DM patients who are being treated at a public hospital in Lima, Peru. Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glucose, glycosylated hemoglobin (HbA1c), and lipid profile. Laboratory parameters and blood …

Lipidomic Risk Score Independently And Cost-Effectively Predicts Risk Of Future Type 2 Diabetes: Results From Diverse Cohorts, Manju Mamtani, Hemant Kulkarni, Gerard Wong, Jacquelyn M. Weir, Christopher K. Barlow, Thomas D. Dyer, Laura Almasy, Michael C. Mahaney, Anthony G. Comuzzie, David C. Glahn, Sarah Williams-Blangero, Ravindranath Duggirala, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening.

Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The …