Informing the Development of a Culturally-Sensitive, Genotype-Informed Intervention for Treatment of Nonalcoholic Fatty Liver Disease in Mexican-Origin Women

Abstract

Given the alarming rates of nonalcoholic fatty liver disease (NAFLD) in Mexican-origin women, there is a dire need to develop personalized, culturally-sensitive interventions in this largely understudied population. National estimates of NAFLD prevalence indicate that Mexican-origin women suffer disproportionately relative to other racial groups, including other US-based Hispanic subgroups. Accordingly, risk factors for NAFLD include obesity and type 2 diabetes, both of which are highly prevalent in Mexican-origin women. Risk of NAFLD is further increased in Mexican-origin women by a greater frequency of a single nucleotide polymorphism, rs738409, occurring in the PNPLA3 gene, which represents an Ile148Met substitution (C>G). This allele confers a substantially greater susceptibility to NAFLD and various stages of progressive NAFLD, including risk and severity of cirrhosis and hepatocellular carcinoma. In the absence of pharmaceutical agents, lifestyle interventions targeting modest weight loss (approximately 5% body weight) have been shown to result in significant clinical reductions in liver fat. Interestingly, treatment response to dietary interventions, independent of weight loss, has been previously shown to be modified by PNPLA3 genotype status in Hispanic pediatric populations and non-Hispanic White adult populations; however, the mechanisms underpinning these effects remain largely unknown. This highlights an important research gap that when addressed, will add to our understanding of how PNPLA3 genotype may modify response to dietary interventions aimed at reducing levels of hepatic steatosis in Mexican-origin adults. Additionally, limited qualitative research has been conducted in the area of NAFLD health risk among Mexican-origin women to inform the development of future interventions in this population. This type of research is needed to add nuance to our understanding of perceived risk and levels awareness and knowledge related to NAFLD among Mexican-origin women. Accordingly, the objective of this dissertation was to accomplish the following: 1) systematically review the state of existing weight loss interventions for U.S. Hispanic women so that future interventions aimed at treating NAFLD can effectively build upon the literature, 2) assess whether PNPLA3 genotype modifies the relationship between dietary factors and levels of hepatic steatosis in a sample of Mexican-origin adults, and 3) ascertain levels of awareness and knowledge related to NAFLD risk among Mexican-origin women as well as perceptions related to NAFLD and liver disease more broadly. Overall, findings from this dissertation included the following: 1) there is a dearth of rigorous randomized controlled trials targeting dietary and physical activity behaviors in U.S. Hispanic women, however existing interventions highlight several considerations for future NAFLD interventions in this population, 2) no significant interactions between PNPLA3 genotype status and dietary intake were identified among our sample of Mexican-origin adults, however, efforts to enhance and replicate the study are warranted, and 3) low levels of NAFLD awareness and knowledge may contribute to misperceptions related to NAFLD risk factors and low perceived risk of liver disease among Mexican-origin women. Findings from this dissertation serve to inform the development of future personalized, culturally-sensitive interventions aimed at treating NAFLD in Mexican-origin women.