U.S. flagAn official website of the United States government
                    Here's how you know **Official websites use .gov**
                            
                            A **.gov** website belongs to an official government organization in the United States.
 **Secure .gov websites use HTTPS**
                            
                            A **lock** (                            
                              A locked padlock                                                      
                            
                            ) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.


Menu Agricultural Research Service
						
                    U.S. DEPARTMENT OF AGRICULTURE
 Food Components and Health Laboratory: Beltsville, MD
 close



    Research

                    Research Projects
                                    Publications
                                    Collaborations
                                    News
                People

                    Staff Listing
                                    Careers


        


                    FCHL Home
                    About FCHL
                        News
                                    Documents
                                    Directions to FCHLSearch small
                    Search
            
            ARS Home
                                About ARS
                                Contact Us




ARS Home Northeast Area Beltsville, Maryland (BHNRC) Beltsville Human Nutrition Research Center Food Components and Health Laboratory Research Publications at this Location





- ARS National Programs
- Search for a scientific manuscript
- Search for a research project
- ARS Software
- Programs and Projects
- Collaborations
- Subjects of Investigation
- Publications

Title:   Author  item
                                            MACKAY, DYLAN - University Of Manitobaitem
                                            ECK, PETER - University Of Manitobaitem
                                            Gebauer, Sarahitem
                                            Baer, Daviditem
                                            JONES, PETER - University Of Manitoba
  Submitted to: The American Journal of Clinical Nutrition
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/31/2015
                                    Publication  Date: 10/1/2015
                                    Citation: Mackay, D.S., Eck, P.K., Gebauer, S.K., Baer, D.J., Jones, P.J. 2015. CYP7A1-rs3808607 and APOE isoform associate with LDL cholesterol lowering after plant sterol consumption in a randomized clinical trial. American Journal of Clinical Nutrition. 102:951-957.Interpretive Summary: Plant sterols lower LDL-cholesterol but there is large variability in the response among individuals.  The variability may be due to small differences in genetic make-up (single nucleotide polymorphisms).  We studied the effect of selected gene polymorphisms on cholesterol response to plant sterols in a study which recruited individuals who were classified as either having a high or low ability to synthesize their own cholesterol.  Adults who had mild elevation of their LDL-cholesterol were selected and classified as having either high (n=24) cholesterol synthesis or low endogenous cholesterol synthesis (n=39) based on their lathosterol to cholesterol (L/C) ratio.  They consumed 2 g/d of plant sterol or a placebo for 28 days. Cholesterol synthesis and change in cholesterol absorption were measured using stable isotope tracers. Candidate genes for single nucleotide polymorphisms and ApoE isoform were assessed. As anticipated, cholesterol fractional synthesis rate was higher in high cholesterol synthesizing participants than in the low synthesizing participants during both placebo and the plant sterol periods of consumption.  LDL-cholesterol lowering in response to plant sterol consumption indeed was associated with individuals’ genotypes. SNP rs3808607-T/T homozygotes showed no LDL-cholesterol lowering, while the presence of the G allele was associated with LDL-cholesterol response in a dose dependent fashion. Similarly, ApoE e3 carriers responded less than ApoE e4 carriers.  Moreover, the gene combination of CYP7A1-SNP-rs3808607-T/T/ApoE e3 was associated with non-responsiveness.  rs5882 in CETP and rs4148217 in ABCG8 did not associate with LDL-cholesterol lowering. Cholesterol absorption was decreased due to plant sterol consumption, but was not related to circulating LDL-cholesterol concentrations, cholesterol synthesis phenotype or genotypes. rs3808607 and ApoE isoform are associated with the extent of reduction in circulating LDL-cholesterol in response to plant sterol consumption and could serve as potential predictive genetic markers to identify individuals who would derive maximum LDL-cholesterol lowering with plant sterol consumption.  These data are of interest to food manufacturers, allied health and medical professionals, and consumers.
                                Technical Abstract: The benefits of plant sterols (PS) for cholesterol lowering are hampered by large heterogeneity across individuals, potentially due to genetic polymorphisms. We investigated the impact of candidate genetic variations on cholesterol response to PS, in a trial which recruited individuals with high or low endogenous cholesterol synthesis, estimated by lathosterol to cholesterol (L/C) ratio. Mildly hypercholesterolemic adults pre-selected as possessing either high endogenous cholesterol synthesis (HS, n=24, L/C=2.03 ± 0.39μmol/mmol) or low endogenous cholesterol synthesis (LS, n=39, L/C=0.99±0.28μmol/mmol) consumed 2g/d of PS or a placebo for 28 days using a dual-center, single-blind, randomized, crossover design. Cholesterol synthesis and change in cholesterol absorption was measured using stable isotopic tracers. Candidate SNPs and ApoE isoform were assessed by TaqMan genotyping assay. Cholesterol fractional synthesis rate (FSR) was higher in HS participants than LS participants during both placebo and PS period. LDL-C lowering in response to PS associated with individuals’ genotypes. SNP rs3808607-T/T homozygotes showed no LDL-C lowering (-0.05±0.07 mmol/L, p=0.9999, n=20), while the presence of the G allele associated with LDL-C response in a dose dependent fashion (G/T: -0.22±0.06 mmol/L, p=0.0006, n=35; G/G: -0.46±0.12 mmol/L, p=0.0009, n=8). Similarly, ApoE e3 carriers (-0.13 ± 0.05 mmol/L, p=0.0370, n=40) responded less than ApoE e4 carriers (-0.31±0.07 mmol/L, p<.0001, n=23). Moreover, genoset CYP7A1-SNP-rs3808607-T/T/ApoE e3 associated with non-responsiveness (+0.09±0.08 mmol/L, p=0.9999, n=14). rs5882 in CETP and rs4148217 in ABCG8 did not associate with LDL-C lowering. Cholesterol absorption was decreased due to PS consumption, but was not related to circulating LDL-C concentrations, cholesterol synthesis phenotype or genotypes.  rs3808607 and ApoE isoform are associated with the extent of reduction in circulating LDL-C in response to PS consumption and could serve as potential predictive genetic markers to identify individuals who would derive maximum LDL-C lowering with PS consumption.


Return to top


Connect with ARS Sign up


ARS Home
                            USDA.gov
                            Plain Writing
                            Policies & Links
                            Civil Rights Statements
                            FOIA
                            Accessibility Statement
                            Privacy Policy
                            Non-Discrimination Statement
                            Quality of Information
                            USA.gov
                            WhiteHouse.gov