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Untargeted Lipidomic Profiling of Human Plasma Reveals Differences due to Race, Gender and Smoking Status

Abstract

Cai X, Perttula K, Pajouh SK, Hubbard A, Nomura DK and Rappaport SM

Lipidomic profiling can link genetic factors and exposures to risks of chronic diseases. Using untargeted liquid chromatography-Fourier Transform mass spectrometry (LC-FTMS), we explored differences in 3,579 lipidomic features in human plasma from 158 non-fasting subjects, pooled by race, gender and smoking status. Significant associations with race (23 features), smoking status (9 features) and gender (2 features) were detected with analysis of variance (ANOVA)-based permutation tests. Identities of several features were confirmed as plasmalogens (vinyl-ether phospholipids) that were present at 2-fold greater concentrations in black subjects. Other putative features, based on accurate masses, were more abundant in white subjects, namely, dihomo-γ-linolenoyl ethanolamide (DGLEA), an endogenous endocannabinoid receptor agonist and a glycerophosphocholine [PC(16:0/18:1)]. After adjustment for race, multivariable linear regression models showed that gender was significantly associated with levels of plasmalogens and DGLEA and that consumption of animal fat was marginally associated with concentrations of plasmalogens. Interestingly, BMI did not explain additional variability in any race-adjusted model. Since plasmalogens are antioxidants that are generally regarded as health-promoting and DGLEA is an agonist of the cannabinoid receptor, our findings that these molecules differ substantially between black and white Americans and between men and women, could have health implications. The concentration of cotinine was greatly elevated in smoking subjects and 6 features with m/z values suggestive of phospholipids or sphingomyelins were present at significantly lower concentrations in smokers.