An estimated 20-30% of the four million Americans with hepatitis C infection (HCV) are projected to develop advanced fibrosis and cirrhosis after 2-3 decades of infection. Differences in exposure to fibrosis-promoting risk factors like alcohol abuse likely explain some of this difference in fibrosis risk. However, current research suggests that genetic factors may also influence the risk of advanced fibrosis in HCV patients. Two factors that research has repeatedly shown to be associated with development of advanced liver disease are male gender and abdominal obesity. However, the specific role genetic factors, including those related to male sex hormone receptor or androgen receptors (AR) and to insulin resistance (IR) associated with abdominal obesity, may play in fibrosis risk remains unclear. The goal of the proposed study is to ascertain the role that changes in AR and IR genes play in increasing risk of advanced fibrosis. The associated specific aims are: 1) to identify and collect data on a large and representative cohort of male veterans with HCV infection;2) to test the hypothesis that 'high risk" variants of genes related to IR either alone or in conjunction with abdominal obesity increase fibrosis risk;and 3) to test the hypothesis that 'high risk'variants of genes related to AR also increase fibrosis risk.
Aim 1 will be accomplished with standard epidemiology methods for cohort identification and will be performed at the Michael E. DeBakey VA.
Aims 2 and 3 will be addressed through a case-control study in which cohort members with advanced fibrosis (cases) are compared to those with mild fibrosis (controls). The research plan, didactic training and outstanding mentoring environment will work together to allow the principal investigator to acquire new skills as well as refine existing skills in the development and execution of novel genetic epidemiology studies, allowing her to develop into an independent investigator in genetic epidemiology of chronic liver and digestive disorders.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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Baylor College of Medicine
Internal Medicine/Medicine
Schools of Medicine
United States
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Kanwal, Fasiha; White, Donna L; Jiao, Li et al. (2015) Genetic Variants in Interleukin-28B Are Associated with Diabetes and Diabetes-Related Complications in Patients with Chronic Hepatitis C Virus Infection. Dig Dis Sci 60:2030-7
White, Donna L; Richardson, Peter; Tayoub, Nabiha et al. (2015) The Updated Model: An Adjusted Serum Alpha-Fetoprotein-Based Algorithm for Hepatocellular Carcinoma Detection With Hepatitis C Virus-Related Cirrhosis. Gastroenterology 149:1986-7
Khalaf, Natalia; White, Donna; Kanwal, Fasiha et al. (2015) Coffee and Caffeine Are Associated With Decreased Risk of Advanced Hepatic Fibrosis Among Patients With Hepatitis C. Clin Gastroenterol Hepatol 13:1521-31.e3
Kanwal, Fasiha; White, Donna L; Tavakoli-Tabasi, Shahriar et al. (2014) Many patients with interleukin 28B genotypes associated with response to therapy are ineligible for treatment because of comorbidities. Clin Gastroenterol Hepatol 12:327-333.e1
Tyson, Gia L; Richardson, Peter A; White, Donna L et al. (2013) Dietary fructose intake and severity of liver disease in hepatitis C virus-infected patients. J Clin Gastroenterol 47:545-52
Luo, Juhua; Chlebowski, Rowan; Liu, Simin et al. (2013) Diabetes mellitus as a risk factor for gastrointestinal cancers among postmenopausal women. Cancer Causes Control 24:577-85
White, D L; Tavakoli-Tabasi, S; Kanwal, F et al. (2013) The association between serological and dietary vitamin D levels and hepatitis C-related liver disease risk differs in African American and white males. Aliment Pharmacol Ther 38:28-37
Liu, Yanhong; El-Serag, Hashem B; Jiao, Li et al. (2013) WNT signaling pathway gene polymorphisms and risk of hepatic fibrosis and inflammation in HCV-infected patients. PLoS One 8:e84407
Li, Linda T; Mills, Whitney L; White, Donna L et al. (2013) Causes and prevalence of unplanned readmissions after colorectal surgery: a systematic review and meta-analysis. J Am Geriatr Soc 61:1175-81
Chen, Brian H; Brennan, Kathleen; Goto, Atsushi et al. (2012) Sex hormone-binding globulin and risk of clinical diabetes in American black, Hispanic, and Asian/Pacific Islander postmenopausal women. Clin Chem 58:1457-66

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