Internal Medicine Commons^™

Factors Associated With Blood Mercury Concentrations And Their Interactions With Three Glutathione S-Transferase Genes (Gstt1, Gstm1, And Gstp1): An Exposure Assessment Study Of Typically Developing Jamaican Children, Sheikh Farzana Zaman, Maureen Samms-Vaughan, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare Pellington, Katherine A Loveland, Mohammad H Rahbar

Journal Articles

BACKGROUND: Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.

METHODS: In this exposure assessment study we used data from 375 typically developing (TD) 2-8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general …

Type 2 Diabetes Modifies The Association Of Cad Genomic Risk Variants With Subclinical Atherosclerosis, Natalie R Hasbani, Kenneth E Westerman, Soo Heon Kwak, Han Chen, Xihao Li, Daniel Di Corpo, Jennifer Wessel, Joshua C Bis, Chloè Sarnowski, Peitao Wu, Lawrence F Bielak, Xiuqing Guo, Nancy Heard-Costa, Gregory L Kinney, Michael C Mahaney, May E Montasser, Nicholette D Palmer, Laura M Raffield, James G Terry, Lisa R Yanek, Jessica Bon, Donald W Bowden, Jennifer A Brody, Ravindranath Duggirala, David R Jacobs, Rita R Kalyani, Leslie A Lange, Braxton D Mitchell, Jennifer A Smith, Kent D Taylor, April P Carson, Joanne E Curran, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Richard A Gibbs, Namrata Gupta, Sharon L R Kardia, Brian G Kral, Zeineen Momin, Anne B Newman, Wendy S Post, Karine A Viaud-Martinez, Kendra A Young, Lewis C Becker, Alain G Bertoni, John Blangero, John J Carr, Katherine Pratte, Bruce M Psaty, Stephen S Rich, Joseph C Wu, Rajeev Malhotra, Patricia A Peyser, Alanna C Morrison, Ramachandran S Vasan, Xihong Lin, Jerome I Rotter, James B Meigs, Alisa K Manning, Paul S De Vries

Journal Articles

BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.

METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 …

Development Of Competency-Based Online Genomic Medicine Training (Cogent)., Susanne B Haga, Wendy K Chung, Luis A Cubano, Timothy B Curry, Philip E Empey, Geoffrey S Ginsburg, Kara Mangold, Christina Y Miyake, Siddharth K Prakash, Laura B Ramsey, Robb Rowley, Carolyn R Rohrer Vitek, Todd C Skaar, Julia Wynn, Teri A Manolio

Journal Articles

The fields of genetics and genomics have greatly expanded across medicine through the development of new technologies that have revealed genetic contributions to a wide array of traits and diseases. Thus, the development of widely available educational resources for all healthcare providers is essential to ensure the timely and appropriate utilization of genetics and genomics patient care. In 2020, the National Human Genome Research Institute released a call for new proposals to develop accessible, sustainable online education for health providers. This paper describes the efforts of the six teams awarded to reach the goal of providing genetic and genomic training …

Further Evidence That Arih1 Rare Variants Predispose To Thoracic Aortic Disease, Maura L Boerio, Nicole M Engelhardt, Sanmati Cuddapah, Jessica I Gold, Isabella C Marin, Amélie Pinard, Dongchuan Guo, Siddharth K Prakash, Dianna M Milewicz

Journal Articles

No abstract provided.

Host And Gut Microbial Tryptophan Metabolism And Type 2 Diabetes: An Integrative Analysis Of Host Genetics, Diet, Gut Microbiome And Circulating Metabolites In Cohort Studies, Qibin Qi, Jun Li, Bing Yu, Jee-Young Moon, Jin C Chai, Jordi Merino, Jie Hu, Miguel Ruiz-Canela, Casey Rebholz, Zheng Wang, Mykhaylo Usyk, Guo-Chong Chen, Bianca C Porneala, Wenshuang Wang, Ngoc Quynh Nguyen, Elena V Feofanova, Megan L Grove, Thomas J Wang, Robert E Gerszten, Josée Dupuis, Jordi Salas-Salvadó, Wei Bao, David L Perkins, Martha L Daviglus, Bharat Thyagarajan, Jianwen Cai, Tao Wang, Joann E Manson, Miguel A Martínez-González, Elizabeth Selvin, Kathryn M Rexrode, Clary B Clish, Frank B Hu, James B Meigs, Rob Knight, Robert D Burk, Eric Boerwinkle, Robert C Kaplan

Journal Articles

OBJECTIVE: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.

METHOD: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.

RESULTS: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with …

Spontaneous Coronary Artery Dissection Is Infrequent In Individuals With Heritable Thoracic Aortic Disease Despite Partially Shared Genetic Susceptibility, Andrea M Murad, Hannah L Hill, Yu Wang, Michael Ghannam, Min-Lee Yang, Norma L Pugh, Federico M Asch, Whitney Hornsby, Anisa Driscoll, Jennifer Mcnamara, Cristen J Willer, Ellen S Regalado, Dianna M Milewicz, Kim A Eagle, Santhi K Ganesh

Journal Articles

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), …

Spotlight On Blisibimod And Its Potential In The Treatment Of Systemic Lupus Erythematosus: Evidence To Date, Aleksander Lenert, Timothy B. Niewold, Petar Lenert

Internal Medicine Faculty Publications

B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF. …