Genetics of LDL particle heterogeneity

Lai

et al. 2016

IJERPH

Elevated LDL-C/HDL-C ratio has been shown to be a marker of lipid metabolism as well as a good predictor of coronary artery disease (CAD). Thus, the aim of this study was to investigate whether the LDL-C/HDL-C ratio is useful for detecting cardiovascular disease (CVD) risk factors in general healthy Uygur adults in Xinjiang. A total of 4047 Uygur subjects aged ě35 years were selected from the Cardiovascular Risk Survey (CRS) study which was carried out from October 2007 to March 2010. Anthropometric data, blood pressure, lipid profile and fasting glucose were measured in all participants. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each LDL-C/HDL-C ratio were calculated. The prevalence of high LDL-C and low HDL-C cholesterol was high and positively correlated with higher LDL-C/HDL-C ratio in the Uygur population. In both men and women, we detected a slight apparent trend of high prevalence of hypertension and hypercholesterolemia with higher LDL-C/HDL-C ratio. Our study also demonstrated that the discriminatory power of the LDL-C/HDL-C ratio for CVD risk factors was slightly stronger in men than in women. Analysis of the shortest distance in the ROC curves for hypertension, dyslipidemia, diabetes, or ětwo of these risk factors suggested a LDL-C/HDL-C ratio cutoff of 2.5 for both men and women. The results of this study showed that a LDL-C/HDL-C ratio cut-off of 2.5 might be used as the predictive marker to detect CVD risk factors among Uygur adults in Xinjiang.

Section: Discussionmentioning

confidence: 99%

Appropriate LDL-C-to-HDL-C Ratio Cutoffs for Categorization of Cardiovascular Disease Risk Factors among Uygur Adults in Xinjiang, China

Lai

et al. 2016

IJERPH

“…Research has suggested that nearly half of the variability in LDL peak particle diameter (LDL-PPD) phenotype is genetically determined [11,12]. However, results from candidate gene and genome-wide association studies (GWAS) have been inconsistent [13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

“…However, results from candidate gene and genome-wide association studies (GWAS) have been inconsistent [13,14,15,16]. Evidence for modest associations with polymorphisms in a number of candidate genes has been reported [11]. Further, genetic variants may exert their effects through interactions with total fat intake.…”

Section: Introductionmentioning

confidence: 99%

Interaction between Common Genetic Variants and Total Fat Intake on Low-Density Lipoprotein Peak Particle Diameter: A Genome-Wide Association Study

et al. 2015

Self Cite

Background/Aim: Total fat intake has an important impact on the low-density lipoprotein (LDL) peak particle diameter (LDL-PPD) and may interact with nutrient-sensitive single nucleotide polymorphisms (SNPs). The objective wasto examine whether there is suggestive evidence of SNP × dietary fat intake interaction effects influencing the LDL-PPD in the Quebec Family Study (QFS) in order to generate hypotheses to be tested in larger studies. Methods: SNPs from a genome-wide association study (GWAS) using Illumina Human610-Quad BeadChip, total fat intake derived from a 3-day weighted food record, and SNP × total fat intake interaction effects were examined on LDL-PPD in 541 QFS subjects. Results: The GWAS analyses 29 identified independent SNP × total fat intake interaction effects on the LDL-PPD at p < 10^-5, including SNPs in the following genes: ABCG2, CPA3, FNBP1, KCNQ3, NBAS, NCALD, OPRL1, NKAIN2, SH3BGRL2, SOX5, and SUSD4. Conclusions: This observational study suggests that multiple SNPs interact with dietary fat intake to influence variation in the LDL-PPD.

“…Since then, the presence of small, dense LDL particles has been associated with a less favorable cardiovascular risk profile [2] and regarded as an emerging risk factor by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III [3]. Although an elevated plasma triglyceride level is a major factor in the formation of small, dense LDL particles, several genetic and environmental factors may also be involved in the modulation of the LDL size phenotype [4,5,6,7]. Among environmental factors, diet has an important impact on LDL peak particle diameter (PPD), one of several features describing LDL size phenotype.…”

Section: Introductionmentioning

confidence: 99%

Effects of Peroxisome Proliferator-Activated Receptors, Dietary Fat Intakes and Gene–Diet Interactions on Peak Particle Diameters of Low-Density Lipoproteins

Bouchard-Mercier

Godin²,

Lamarche

et al. 2011

Lifestyle Genomics

Self Cite

The risk of cardiovascular diseases (CVDs) is modulated by gene–diet interactions. The objective of this study was to examine whether gene–diet interactions affect peak particle diameters (PPD) of low-density lipoprotein (LDL). Methods: The study included 674 participants. A food frequency questionnaire was administered to obtain dietary information. LDL-PPD was determined by non-denaturing 2–16% polyacrylamide gradient gel electrophoresis. Peroxisome proliferator-activated receptor (PPAR) gene polymorphisms PPARα L162V (rs1800206), PPARγ P12A (rs1801282) and PPARδ –87T→C (rs2016520) were determined by PCR-RFLP. Results: Among carriers of thePPARα L162V polymorphism, gene–diet interaction effects on LDL-PPD were observed with saturated fat (p = 0.0005) and total dietary fat (p = 0.006). Among PPARα V162 carriers, subjects with higher saturated fat intakes had smaller LDL-PPD than those with lower intakes (254.23 ± 2.74 vs. 256.21 ± 2.61 Å, respectively, p = 0.007). Among subjects homozygous for the PPARα L162 allele, those with higher saturated fat intakes had larger LDL-PPD than those with lower saturated fat intakes (255.86 ± 2.66 vs. 255.05 ± 2.65 Å, respectively, p = 0.01). Gene–diet interactions were also found for PPARγ P12A polymorphism with saturated fat intake (p = 0.04) and for PPARδ –87T→C with the polyunsaturated/saturated fat ratio (p = 0.0013). Conclusions: These results stress that dietary factors should be included in studies determining the effect of different polymorphisms on CVD risk factors.