Mitochondrial Haplogroups in Obese Patients Predisposed to Non-Alcoholic Fatty Liver Disease (NAFLD)
Date
2014-10-21
Authors
Jeiran, Kianoush
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Abstract
Liver diseases are considered a significant health problem worldwide. 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 the progressive course of NAFLD. In this study, the association of sequence variations (haplogroups) in the control loop of mitochondria was investigated. A total of 115 cases of morbidly obese patients with liver biopsy results were included (average BMI=48.0±11.1; White=80.2%; African-American=17.4%; Females=75.6%). All these patients also had metabolic syndrome. Among 86 profiled individuals, 64 (74.4%) were diagnosed with NAFLD. After extracting DNA from whole blood cells and amplifying 1122 base pairs 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 of 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%) (Fisher’s test, two tailed P= 0.003). Within the major haplogroups, the prevalence of NAFLD varied: H (80.00%), L (38.46%), K (83.33%), J and U (80.00% each) (Fisher’s test two tailed P= 0.068). 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.
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Keywords
Non-alcoholic fatty liver disease, Mitochondrial haplogroups, Obesity and fatty liver disease, Metabolic syndrome and fatty liver disease, Mitochondrial genotype and fatty liver disease