The Impact of FADS Variants on Responses to Diet in Patients With ALI

Abstract

Nutritional support in the intensive care unit (ICU) is a vital element of patient care. Polyunsaturated fatty acids (PUFAs) like γ‐linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been recommended in immunomodulatory diets because of their anti‐inflammatory effects. However, clinical trials have failed to show unanimous benefit with PUFA‐rich diets. Metabolic conversion of these PUFAs are dependent on fatty acid desaturase (FADS) and elongase (ELOVL) enzymes, which are unequal across humans. In fact, several genetic variants within FADS and ELOVL genes have been shown to impact PUFA metabolism. Select variants are also differentially expressed in African Americans. We hypothesize that these genetic variants may help explain the differential responses to PUFA‐rich diets. In this study, we aimed to investigate gene‐diet interactions in patients with acute lung injury (ALI).Banked DNA and plasma samples from the OMEGA randomized clinical trial (NCT00609180) were used to conduct a secondary analysis on genetic variants within FADS and ELOVL regions; 43 SNPs were genotyped. Plasma PUFA levels were quantified using gas chromatography. Of the 272 enrolled, 143 received omega‐rich vs. 129 placebo diets. All statistical analyses were stratified by race and adjusted for age and gender.Several SNPs were associated with PUFA levels. Notably, SNP rs174537 had a significant impact on arachidonic acid (ARA). Caucasian T allele carriers on the omega‐rich diet had lower ARA levels (p=0.022, Fig. 1). Interestingly, this SNP had a major impact on PUFAs within African Americans on both placebo and omega‐rich diets. ARA levels were significantly higher and DHA levels were low (p=0.0007) in African Americans. Genotype at rs174537 was associated with patient outcomes; Caucasians with the T allele had significantly more VENT‐free and ICU‐free days (~>12%) than GGs, but this was not observed within African Americans. Instead, a significant interaction between gender and diet was seen, with African American women on placebo diet having 40% fewer VENT‐free (p=0.009) and ICU‐free days (p=0.022) than African American men. Mortality was highest in GGs receiving omega‐rich diets in both races, however this was not statistically significant. These data suggest strong ethnic, gender and genetic factors influencing the response to omega‐rich diets. Further investigation on other gene‐gene interactions (e.g. between FADS and ELOVL variants), and epigenetic modifications are needed to understand the underlying mechanisms regulating PUFA metabolism and biosynthesis in critically injured and ill patients.Support or Funding InformationNIH K25 HL133611This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Association of the Rs174537 Polymorphism of the Fatty Acid Desaturase 1 and 2 Gene Enhancer (Fads1 and Fads2) With Type 2 Diabetes Mellitus

“…Гены десатуразы жирных кислот 1 и 2 (FADS1 и FADS2) играют решающую роль в метаболизме ПНЖК. Однонуклеотидный полиморфизм (SNP) rs174537, расположенный в энхансере генов FADS1 и FADS2, влияет на уровень арахидоновой кислоты и тесно связан с ферментативной активностью FADS; установлено, что генотип TT (rs174537) фенотипически связан с низкой эффективностью пути биосинтеза ПНЖК в когортах европейцев и афроамериканцев [11]. Частота аллелей полиморфизма rs174537 сильно различается между популяциями [12], что, вероятно, и приводит к различиям в связи ПНЖК и заболеваемостью СД 2-го типа между европейцами и азиатами.…”