Thesis Defense Announcement To: The George Mason University Community Candidate: Kianoush Jeiran Program: M.S. in Biology Date: Thursday June 26, 2014 Time: 1:00 p.m. Place: George Mason University Prince William Campus<http://www.gmu.edu/resources/welcome/Directions-to-GMU.html> Bull Run Hall, Room 246 Title: "Mitochondrial Haplogroups In Obese Patients Predisposed To Non-Alcoholic Fatty Liver (Nafld)" Thesis Director: Dr. Ancha Baranova Thesis Committee: Dr. Alessandra Luchini, Dr. Aybike Birerdinc A copy of the thesis will be available in the Mercer Library. All are invited to attend the defense. ABSTRACT Liver diseases considered a significant health problem worldwide nowadays. Among distinct disease, non-alcoholic fatty liver disease (NAFLD), which is widely considered the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease trait where environment and genetic variations interact to determine the wide spectrum of disease progression. One of the key challenges is to predict the progression of NAFLD. Our central hypothesis is that certain mitochondrial genotype or genotypes may serve as an indicator of increased susceptibility to progressive course NAFLD. In this study, the association of sequence variations (haplogroups and indels) in the control loop of mitochondria was investigated. A total of 86 cases of morbidly obese patients with liver biopsy results were included (average BMI=48; White=80.2%; African-American=17.4%; Females=75.6%). All these patients also had a metabolic syndrome. Among 86 profiled individuals, 64 (74.4%) were diagnosed with NAFLD. After extracting DNA from whole blood cells and amplifying 1122 base pair of control loops by PCR and Sanger sequencing, all samples have been categorized into one of 11 haplogroups (H, L, K, U, J, T, M, W, N, C, and X). The most common haplogroup in this study (34.9%) was H haplogroup, while other haplogroups including L (15.1%), K (13.95%), U (11.6%), J (11.6%), T (7.0%), M, W, N, C, and X (1.2% each) were less common. The presence NAFLD was found to be associated significantly with non-L haplogroups (H, K, T, C, U, M, N, J, W, X) (80.84% vs 38.4%) (chi square=10.4, P<0.001). Within the major haplogroups, the prevalence of NAFLD varied: H (80.00%), L (38.46%), K (83.33%), J and U (80% each) (chi square=9.83, P=0.043). Moreover, within L haplogroups, L3 shows the least tendency to develop NAFLD. Further investigations are warranted to assess why in individuals with East African L3 haplogroup, the susceptibility to NAFLD is reduced. ###