Abstract
BackgroundLDL cholesterol (LDL-C) concentration is modified by dietary and genetic factors; however, little is known about the details of this relationship. Our aim was to investigate the associations taking into account dietary assessment methods, seasonal effects and missing values.MethodsStudy subjects completed food frequency questionnaires (FFQ) and supplied 3-day weighed dietary records (WDRs) and blood samples in four seasons. Approximately 660,000 single nucleotide polymorphisms (SNPs) were measured. Candidate SNPs related to LDL-C concentration were systematically selected. Multiple imputation was applied for missing values. A total of 312 repeated measures data were used for analyses. After adjusting for season and subjects as fixed and random effects, effects of nutrient intake and SNPs on LDL-C concentration were assessed according to three dietary assessment methods: the FFQ and first and four season 3-day WDRs (4 s-3d WDRs).ResultsFor LDL-C concentration, ethanol consumption derived from all three dietary assessment methods was consistently associated (P < 0.09 for all). Positive and negative relationships were consistently shown with rs651007 and rs1160985 in the first and four seasons; but the latter remained after adjusting for total dietary fiber intake derived from the FFQ and 4 s-3d WDRs (P < 0.05, excepting the first 3-day WDRs). rs599839 was negatively associated after cholesterol intakes derived from the first and 4 s-3d WDRs were considered (P < 0.05 and 0.07, respectively). Each rs17145738 and ethanol consumption based on the 4 s-3d WDRs was related to LDL-C concentration (P < 0.05). Seasonal variations of LDL-C concentration were observed only in summer.ConclusionsIn contrast to nutrient intake, ethanol consumption was shown to be comprehensively related to LDL-C concentration, regardless of dietary assessment methods. Taking into account seasonal effects, critical relationships with LDL-C concentration for some SNPs, after adjustment for specific nutrients, were revealed. Our findings can be used to help to interpret the relationships between dietary and genetic factors on LDL-C concentration in large-scale epidemiological studies.(10/10 keywords)
Highlights
LDL cholesterol (LDL-C) concentration is modified by dietary and genetic factors; little is known about the details of this relationship
According to mixed-effect models, seasonal variations were shown in LDL-C, total and HDL cholesterol (P < 0.05 for all) (Table 1), and the values were lower in summer
In the cross-sectional study, using a multiple regression model, LDL-C concentration was found to have a negative association with total dietary fiber (TDF) intake only in the Complete case (CC) dataset (P = 0.02)
Summary
LDL cholesterol (LDL-C) concentration is modified by dietary and genetic factors; little is known about the details of this relationship. Our aim was to investigate the associations taking into account dietary assessment methods, seasonal effects and missing values. Higher concentration of LDL cholesterol (LDL-C) is an important risk factor for developing CVD and an important target for treatment [2, 3]. The highest risk for hypercholesterolemia has been reported to occur in winter [4, 5] For this reason, the season in which health examinations are undergone might result in under- or over-estimation of LDL-C concentration [5]. A negative association with LDL-C concentration has been inconsistent for moderate alcohol consumption, yet [6], and studies to date have failed to show that such reduction in dietary intake is effective. Some FFQs have been developed that take seasonal variation into account [10, 11]
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