Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism

Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE

Identification of eQTLs for Hepatic Xbp1s and Socs3 Gene Expression in Mice Fed a High-Fat, High Caloric Diet

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent form of human hepatic disease and feeding mice a high-fat, high-caloric (HFHC) diet is a standard model of NAFLD. To better understand the genetic basis of NAFLD, we conducted an expression quantitative trait locus (eQTL) analysis of mice fed a HFHC diet. Two-hundred sixty-five (A/J × C57BL/6J) F2 male mice were fed a HFHC diet for 8 wk. eQTL analysis was utilized to identify genomic regions that regulate hepatic gene expression of Xbp1s and Socs3. We identified two overlapping loci for Xbp1s and Socs3 on Chr 1 (164.0–185.4 Mb and 174.4–190.5 Mb, respectively) and Chr 11 (41.1–73.1 Mb and 44.0–68.6 Mb, respectively), and an additional locus for Socs3 on Chr 12 (109.9–117.4 Mb). C57BL/6J-Chr 11A/J/ NaJ mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3 gene expression (P \u3c 0.05), whereas C57BL/6J-Chr 1A/J/ NaJ mice retained the C57BL/6J phenotype. In addition, we replicated the eQTLs on Chr 1 and Chr 12 (LOD scores ≥3.5) using mice from the BXD murine reference panel challenged with CCl4 to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs for Xbp1 and Socs3on Chr 1 and Chr 11, and consomic mice confirmed that replacing the C57BL/6J Chr 11 with the A/J Chr 11 resulted in an A/J phenotype for Xbp1 andSocs3 gene expression. Identification of the genes for these eQTLs will lead to a better understanding of the genetic factors responsible for NAFLD and potentially other hepatic diseases

Fiery Wives And Icy Husbands: Pre-Marital Counseling And Covenant Marriage As Buffers Against Effects Of Childhood Abuse On Gendered Marital Communication?

We examine relationships between childhood abuse and two maladaptive marital communication patterns - hostile and withdrawing - and test whether covenant marriage or pre-marital counseling mediate the effects of childhood abuse. Drawing on a sample from the Marriage Matters (1997-2004) data, we find both gendered differences in communication and in the relationship between childhood abuse and negative communication patterns. Wives are more likely to use a hostile style of communication, whereas husbands are more likely to use a withdrawing style. We also find that childhood abuse affects hostile communication for both spouses but influences only wives\u27 withdrawing. Neither covenant marriage nor pre-marital counseling is associated with hostile communication for either spouse. Covenant marriage increases husbands\u27 withdrawal from conflict, whereas pre-marital counseling increases the use of withdrawing communication in both wives and husbands. © 2010 Elsevier Inc

State-Based Surveillance for Selected Hemoglobinopathies

Purpose: The lack of an ongoing surveillance system for hemoglobinopathies in the United States impedes the ability of public health organizations to identify individuals with these conditions, monitor their health-care utilization and clinical outcomes, and understand the effect these conditions have on the health-care system. This article describes the results of a pilot program that supported the development of the infrastructure and data collection methods for a state-based surveillance system for selected hemoglobinopathies. Methods: The system was designed to identify and gather information on all people living with a hemoglobinopathy diagnosis (sickle cell diseases or thalassemias) in the participating states during 2004–2008. Novel, three-level case definitions were developed, and multiple data sets were used to collect information. Results: In total, 31,144 individuals who had a hemoglobinopathy diagnosis during the study period were identified in California; 39,633 in Florida; 20,815 in Georgia; 12,680 in Michigan; 34,853 in New York, and 8,696 in North Carolina. Conclusion: This approach provides a possible model for the development of state-based hemoglobinopathy surveillance systems

Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism

INTRODUCTION: Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE. OBJECTIVES: To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. PATIENTS/METHODS: We studied 107 patients with VTE separated into 3 groups: (1) ‘low-risk’ patients had one or more provoked VTE; (2) ‘moderate-risk’ patients had a single unprovoked VTE; (3) ‘high-risk’ patients had ≥2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12 V4 Beadchips to assay whole genome expression. RESULTS: Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC = 0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC’s of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups. CONCLUSION: Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons