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RAS Guanyl Releasing Protein 4 Polymorphisms and Brain Outcomes Across the Alzheimer's Spectrum

Undergraduate #95
Discipline: Biological Sciences
Subcategory: Genetics

Ana Collazo Martinez - Iowa State University
Co-Author(s): Auriel Willette, PhD, MS, Department of Food Science and Human Nutrition, Department of Psychology, Iowa State University, Ames, IA Aging Mind and Brain Institute, University of Iowa, Iowa City, IA



Neuroinflammation plays a key role in many neurodegenerative diseases. It is relatively unknown how genetic polymorphisms for neuroinflammatory genes may affect gray matter (GM) volume and glucose metabolism. Among 463 subjects, we investigated differences between polymorphisms at RS3810342 coding for RAS guanyl releasing protein 4 (RasGRP4), which regulates the expression of prostaglandin D2 in mast cells. Free Surfer cortical thickness values where used. PLINK identified and extracted the variant . Subsequent GM analyses were done in SPM12. Inflammatory, cognitive, and Alzheimer’s Disease (AD) biomarkers analyses were done in SPSS. Minor allele carriers had less GM throughout neocortex, particularly in prefrontal areas (k=110658 voxels). The variant also predicted higher C-reactive protein (p=0.023) and IL-16 (p=0.048). No associations with cognitive scores or AD biomarkers were found. Overall, these preliminary data show a significant novel association of a recently discovered gene variant for neuroinflammation with regional GM and inflammation markers, which might be relevant in the study of neuroinflammation in neurodegenerative diseases.

RasGRP4_Abstract_Final.docx

Funder Acknowledgement(s): IINSPIRE LSAMP supported by NSF Award Number: HRD-1102461

Faculty Advisor: Dr. Auriel Willette, awillett@iastate.edu

Role: Study design and analyses

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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