This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Since our laboratory's initial linkage of Type 2 diabetes to a mtDNA rearrangement in a three generation maternal pedigree 13 years ago, there has been increasing support for our hypothesis that mitochondrial dysfunction plays an important role in the etiology of Type 2 Diabetes Mellitus (DM) and the overlapping Metabolic Syndrome (MS). With this study we are planning to substantially expand upon the existing knowledge in the field by an extensive investigation of defects in mitochondrial oxidative phosphorylation (OXPHOS) caused potentially by deleterious sequence variants in the mitochondrial DNA (mtDNA). These diabetogenic mtDNA variants are proposed to range from recent, relatively severe, mutations resulting in substantial OXPHOS defects with familial DM &MS to ancient, relatively mild, polymorphisms that result in partial OXPHOS defects and an increase in the risk to develop DM &MS. To test this hypothesis, we propose to analyze the mtDNAs of an existing collection of samples from Taiwan Chinese families, which exhibit maternal transmission of DM &MS as well as approximately 500 Taiwan Chinese DM/MS non familial cases and controls to identify causal pathogenic mtDNA mutations. The study is designed to look for associations between the common Asian mtDNA lineages (haplogroups) and predisposition to MS and DM. The Taiwanese cohort of samples will not be included under this IRB application but will fall under a separate, exempt status application which has been submitted to the Investigational Review Board. (application submitted 11/01/05).

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000827-35
Application #
8166909
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2009-12-01
Project End
2010-06-30
Budget Start
2009-12-01
Budget End
2010-06-30
Support Year
35
Fiscal Year
2010
Total Cost
$38,831
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H et al. (2018) Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int 93:1442-1451
Lavigne, Katie M; Woodward, Todd S (2018) Hallucination- and speech-specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task-based fMRI data: An fBIRN study. Hum Brain Mapp 39:1582-1595
Milot, Marie-Hélène; Marchal-Crespo, Laura; Beaulieu, Louis-David et al. (2018) Neural circuits activated by error amplification and haptic guidance training techniques during performance of a timing-based motor task by healthy individuals. Exp Brain Res 236:3085-3099
Hsu, Simon; Rifkin, Dena E; Criqui, Michael H et al. (2018) Relationship of femoral artery ultrasound measures of atherosclerosis with chronic kidney disease. J Vasc Surg 67:1855-1863.e1
Inker, Lesley A; Grams, Morgan E; Levey, Andrew S et al. (2018) Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium. Am J Kidney Dis :
Egnot, Natalie Suder; Barinas-Mitchell, Emma; Criqui, Michael H et al. (2018) An exploratory factor analysis of inflammatory and coagulation markers associated with femoral artery atherosclerosis in the San Diego Population Study. Thromb Res 164:9-14
Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671
Chen, Teresa K; Appel, Lawrence J; Grams, Morgan E et al. (2017) APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension). Arterioscler Thromb Vasc Biol 37:1765-1769
Juraschek, Stephen P; Appel, Lawrence J; Miller 3rd, Edgar R (2017) Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension. Am J Hypertens 30:871-875
Chen, Teresa K; Tin, Adrienne; Peralta, Carmen A et al. (2017) APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD. Clin J Am Soc Nephrol 12:1771-1777

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