The overall objective of this study is to determine pro-inflammatory cytokine allele frequencies in West Africans and African Americans with NIDDM and to determine the linkage of these alleles to clinical phenotypes of NIDDM. Specifically we will 1) determine the frequency of allelic polymorphisms in the TNF-a gene promoter (-238, -308), IL-6 gene promoter (174) and IL-1b gene promoter (-511); and their receptor gene polymorphisms (TNFR-1, TNFR-2 593-598-620); and the association of these alleles with insulin sensitivity and BMI in a cohort of West Africans and a subgroup of African Americans with NIDDM. 2) to determine cytokine and cytokine receptor gene expression relative to their promoter polymorphisms, insulin sensitivity and BMI phenotypes; 3) to determine plasma cytokine and soluble receptor ;levels in the AADM, recruited control sets, in LPS-treated GENNID diabetic samples and control sets. Increasing evidence exists that TNF-a, IL-6 and IL-1b play a key role in obesity and insulin resistance. Obesity and insulin resistance are hallmarks of NIDDM. Because of their regulatory role in the immune system and also in the endocrine system, cytokines have become significant markers for genetic and functional studies. Most genetic studies of obesity and NIDDM are performed with samples from Caucasian populations while are few studies on African Americans and a paucity of information on Africans, considering the global nature of this disease. This study will be the largest and most comprehensive study of the genetics of cytokine polymorphisms in NIDDM in Africans and African Americans thus far. Data from these studies may provide insights into the relationships, if any, between Americans and their ancestral counterparts as it relates to the activity of these cytokine genes in NIDDM.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
2S06GM008016-32
Application #
6547809
Study Section
Special Emphasis Panel (ZGM1)
Project Start
1977-06-01
Project End
2006-07-31
Budget Start
Budget End
Support Year
32
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Howard University
Department
Type
DUNS #
056282296
City
Washington
State
DC
Country
United States
Zip Code
20059
Faruque, Mezbah U; Chen, Guanjie; Doumatey, Ayo P et al. (2017) Transferability of genome-wide associated loci for asthma in African Americans. J Asthma 54:1-8
Johnston, Henry Richard; Hu, Yi-Juan; Gao, Jingjing et al. (2017) Identifying tagging SNPs for African specific genetic variation from the African Diaspora Genome. Sci Rep 7:46398
Rand, Kristin A; Rohland, Nadin; Tandon, Arti et al. (2016) Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk. Hum Mol Genet 25:371-81
Mathias, Rasika Ann; Taub, Margaret A; Gignoux, Christopher R et al. (2016) A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome. Nat Commun 7:12522
Ehret, Georg B (see original citation for additional authors) (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 48:1171-1184
Kurian, P; Dunston, G; Lindesay, J (2016) How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases. J Theor Biol 391:102-12
Kessler, Michael D; Yerges-Armstrong, Laura; Taub, Margaret A et al. (2016) Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry. Nat Commun 7:12521
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
Ogunjirin, Adebowale E; Fortunak, Joseph M; Brown, LaVerne L et al. (2015) Competition, Selectivity and Efficacy of Analogs of A-84543 for Nicotinic Acetylcholine Receptors with Repositioning of Pyridine Nitrogen. Neurochem Res 40:2131-42
Winchester, Danyelle; Ricks-Santi, Luisel; Mason, Tshela et al. (2015) SPINK1 Promoter Variants Are Associated with Prostate Cancer Predisposing Alterations in Benign Prostatic Hyperplasia Patients. Anticancer Res 35:3811-9

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