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A Combination of Single Nucleotide Polymorphisms is Associated with the Interindividual Variability of Cholesterol Bioavailability in Healthy Adult Males
Author(s) -
Desmarchelier Charles,
Wolff Estelle,
Defoort Catherine,
Nowicki Marion,
Morange PierreEmmanuel,
Alessi MarieChristine,
Valéro René,
Nicolay Alain,
Lairon Denis,
Borel Patrick
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202000480
Subject(s) - single nucleotide polymorphism , bioavailability , cholesterol , biology , genetics , medicine , endocrinology , gene , genotype , pharmacology
Scope Cholesterol bioavailability displays a high interindividual variability, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explained a minor fraction of the variability of this complex phenotype. The aim is to identify a combination of SNPs associated with a significant part of the variability in cholesterol bioavailability. Methods and results Thirty‐nine healthy adult males are given a standard test snack containing 80 mg heptadeuterated (D7) cholesterol. The plasma D7‐cholesterol concentration is measured at equilibrium 40 h after test snack intake. The D7‐cholesterol response (D7‐cholesterol/total cholesterol concentration) exhibits a relatively high interindividual variability (CV = 32%). The association of exonic SNPs in candidate genes (188 genes involved in or related to cholesterol metabolism) with the plasma D7‐cholesterol response is assessed by univariate statistics followed by partial least squares regression. A significant model ( p ‐value after cross‐validation ANOVA = 1.64 × 10 −7 ) that includes 8 SNPs ( SOAT2 ‐rs9658625, DNAH11 ‐rs11768670, LIPC ‐rs690, MVK ‐rs2287218, GPAM ‐rs10787428, APOE ‐rs7412, CBS ‐rs234706, and WRN ‐rs1801196) explains 59.7% of the variance in cholesterol bioavailability (adjusted R ²). Conclusion Here a combination of SNPs is significantly associated with the variability in dietary cholesterol bioavailability in healthy adult males.