Presentation description

Background & Objective:
ASAH2 is a genetic mutation that was originally identified in five Native Hawaiian and Pacific Islander (NHPI) individuals who had diabetes, obesity, or kidney failure. In these carriers, they have exhibited higher levels of circulating ceramides compared to non-carriers with similar clinical profiles. This observation has prompted further investigation into lipidomic differences in a larger community-based cohort. The main objective is to determine whether carriers of the ASAH2 mutation have elevated ceramide levels compared to non-carries within the Utah Pacific Islander Diabetes Study (UPIDS) cohort of NHPI individuals.

Methods:
We will perform SNP genotyping (qPCR) on DNA samples from several hundred UPIDS participants to identify ASAH2 mutation carriers. Genotyping data will be matched to existing lipidomics data. Circulating ceramides will be plotted by carrier status, and linear regression models will be used to assess the relationship between ASAH3 mutation and ceramide levels while adjusting for covariates such as age, sex, and BMI. This data will then be compared to already completed mouse data of similar clinical aspects.

Outcomes:
We anticipate that the ASAH2 mutation carrier will exhibit significantly higher levels of circulating ceramides compared to non-carriers. These findings could reveal a potential genetic contribution to lipid dysregulation in NHPI individuals with metabolic disease and guide future precision health approaches.