This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The proposed research is designed to determine the prevalenc and risk factors of pulmonry hypertension (PHTN) in children and adolescents with sickle cell disease (SCD), and to determine the role of the hypoxic response in it s pathogenesis. The present proposal is based on three postulates. First, the problem of SCD-associated PHTN may begin during childhood and adolescence. Second, the pathogenesis of SCD-associated PHTN may include not only the effects of nitric oxide scavenging in a chronic hemolytic disorder, but also the consequences of chronic hypoxia related to severe anemia and to repeated vasoocclusive episodes. PHTN is a complication of conditions marked by chronic hypoxia, and aslo a complication of Chuvash polycythemia (CP), a congenital disorder of oxygen sensing in which the hypoxic response is constitutively up regulated in the absence of hypoxia. Third, we postulate that the pathophysiology of SCD-associated PHTN may be elucidated by comparing proliferative vascular responses medicated by HIF and by nitric oxide scavenging in patients with SCD and CP according to the presence or absence of pulmonary hypertension. Based on a comparison of the clinical and pathophysiologic features of SCD and CP, we hypothesize that, in addition to increased nitric oxide-scavenging, altered expression of a gene or genes regulated by hypoxia inducible factor (HIF) is central to the pathophysiology of PHTN in both SCD and CP.
Aim 1. Determine the prevalence, risk factors and clinical consequences of pulmonary hypertension (PHTN) in children and adolescents with sickle cell disease (SCD).
Aim 2. Elucidates the pathophysiology of PHTN in SCD by comparing proliferative vascular resonses mediated by 1) HIF and 2) nitric oxide-scavenging form the clinical to cellular level in patiens with SCD and patients with Chuvash polycythemia (CP).
Aim 3. Using mircro array analysis and high throughput genotyping, examine patterns of gene expression and candiadate gene polymorphisms of the HIF-mediated hypoxi response in SCD and CP patients with and without PHTN.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
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Howard University
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Christensen, Kurt D; Uhlmann, Wendy R; Roberts, J Scott et al. (2018) A randomized controlled trial of disclosing genetic risk information for Alzheimer disease via telephone. Genet Med 20:132-141
Doumatey, Ayo P; He, William J; Gaye, Amadou et al. (2018) Circulating MiR-374a-5p is a potential modulator of the inflammatory process in obesity. Sci Rep 8:7680
Guan, Yue; Roter, Debra L; Wolff, Jennifer L et al. (2018) The impact of genetic counselors' use of facilitative strategies on cognitive and emotional processing of genetic risk disclosure for Alzheimer's disease. Patient Educ Couns 101:817-823
Mullins, Tanya L Kowalczyk; Li, Su X; Bethel, James et al. (2018) Sexually transmitted infections and immune activation among HIV-infected but virally suppressed youth on antiretroviral therapy. J Clin Virol 102:7-11
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
Guan, Yue; Roter, Debra L; Erby, Lori H et al. (2017) Disclosing genetic risk of Alzheimer's disease to cognitively impaired patients and visit companions: Findings from the REVEAL Study. Patient Educ Couns 100:927-935
Nandakumar, Priyanka; Lee, Dongwon; Richard, Melissa A et al. (2017) Rare coding variants associated with blood pressure variation in 15?914 individuals of African ancestry. J Hypertens 35:1381-1389
Cain, Gloria E; Kalu, Nnenna; Kwagyan, John et al. (2016) Beliefs and Preferences for Medical Research Among African-Americans. J Racial Ethn Health Disparities 3:74-82
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
Lieberman, Richard; Armeli, Stephen; Scott, Denise M et al. (2016) FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students. Am J Med Genet B Neuropsychiatr Genet 171:879-87

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