Clinical and Genetic Characteristics of Liver Disease among Mexican Americans in South Texas
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease which includes simple steatosis, fibrosis, and cirrhosis, and ultimately increases the risk for hepatocellular carcinoma (HCC). As HCC is increasing in incidence among Hispanics in the United States, detailed understanding of the risk factors—fibrosis and cirrhosis—may improve HCC prevention. In this project, we evaluated the clinical and genetic characteristics associated with liver disease, ranging from steatosis to fibrosis, among Mexican Americans in south Texas, using clinical data including elastographic imaging and single nucleotide polymorphism (SNP) measurements from the Cameron County Hispanic Cohort. First, we quantified ancestral proportions and found that Amerindian ancestry was not strongly associated with liver disease phenotypes, but rather an association between Amerindian ancestry and insulin resistance may partially explain the high rates of NAFLD among Mexican Americans in the US. Second, in a genome-wide association study, we discovered two coding genetic variants that may affect risk of fatty liver and interpretation of liver enzyme levels, while in a candidate gene association study, our elastographic measurements failed to convincingly validate any known liver disease risk variants. Third, we found a robust association between hemoglobin A1c measurements and liver stiffness measured by transient elastograpy, after accounting for biological relatedness. Overall, these studies improve our understanding of the genetic and clinical characteristics of liver disease—primarily due to metabolic dysfunction—in a Mexican American population. Additionally, our results indicate that elastographic imaging may be a promising way forward to elucidate the genetic underpinnings of fibrosis risk, but further longitudinal studies in in distinct cohorts are needed to con. Most importantly, our results reinforce the importance of metabolic disease in the characterization and prevention of liver disease in south Texas.
Watt, Gordon P, "Clinical and Genetic Characteristics of Liver Disease among Mexican Americans in South Texas" (2018). Texas Medical Center Dissertations (via ProQuest). AAI10928067.