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• W4387335734 abstract "Introduction Hypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES). Methods Participants were categorized into the Low-HDL (case; n = 16,980) and Normal-HDL ( n = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (&lt;40 mg/dL for men and &lt; 50 mg/dL for women) and included those taking medication for dyslipidemia. The genes associated with hypo-HDL-C were determined through a genome-wide association study (GWAS) in a city hospital-based cohort, and the results were validated in the Ansan/Anung study. The genetic variants for the single nucleotide polymorphism (SNP)-SNP interaction were selected using a generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS) generated was evaluated for interaction with lifestyle parameters. Results The participants with hypo-HDL-C showed a 1.45 and 1.36-fold higher association with myocardial infarction and stroke, respectively. The High-PRS with four SNPs, namely ZPR1 _rs3741297, CETP _rs708272, BUD13 _rs180327, and ALDH1A2 _rs588136, and that with the 11q23.3 haplotype were positively associated with hypo-HDL-C by about 3 times, which was a 2.4-fold higher association than the PRS of 24 SNP with p &lt; 5×10 −8 . The risk alleles of CETP _rs708272 and ALDH1A2 _rs588136 were linked to increased expression in the heart and decreased in the brain, respectively. The selected SNPs were linked to the reverse cholesterol transport pathway, triglyceride-rich lipoprotein particle remodeling pathway, cholesterol storage, and macrophage-derived foam cell differentiation regulation. The PRS of the 4-SNP model interacted with energy intake and smoking status, while that of the haplotype interacted with a glycemic index of the diet, sulfur microbial diet, and smoking status. Discussion Adults with a genetic risk for hypo-HDL-C need to modulate their diet and smoking status to reduce their risk." @default.
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• W4387335734 date "2023-10-04" @default.
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• W4387335734 title "Interaction of energy and sulfur microbial diet and smoking status with polygenic variants associated with lipoprotein metabolism" @default.
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• W4387335734 doi "https://doi.org/10.3389/fnut.2023.1244185" @default.
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