在高甘油三酯血症中整合遗传学和精确营养的生活方式:英国生物银行和KoGES分析。

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Haeng Jeon Hur, Hye Jeong Yang, Min Jung Kim, Hyun-Jun Jang, Myung-Sunny Kim, Sunmin Park
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引用次数: 0

摘要

背景:高甘油三酯血症是心血管疾病的独立危险因素。目的:本研究利用英国生物银行(n = 479,300)和韩国基因组与流行病学研究(KoGES;N = 57,939)。方法:根据200 mg/dL以上的空腹血清TG浓度对高TG组进行分类(高加索人,UK Biobank, n = 100,543;韩国人,KoGES, n = 7211)。多基因风险评分(PRS)是通过全基因组关联研究(GWAS)和广义多因素降维(GMDR)分析确定的遗传变异中的风险等位基因来计算的。结果:韩国人GCKR、APOA5、SIK3和APOE基因的风险等位基因频率高于白种人。在调整协变量后,包括脂蛋白脂肪酶(LPL)_rs328、载脂蛋白A5 (APOA5)_rs2072560和葡萄糖激酶调节因子(GCKR)_rs780093在内的PRS分别显示白种人和韩国人的高tg风险增加2.2倍(UK Biobank)和2.6倍(KoGES)。在这两个队列中,PRS与代谢综合征、血清低高密度脂蛋白(HDL)-胆固醇和高低密度脂蛋白(LDL)-胆固醇浓度呈正相关,但与高tg呈负相关。在基因组注释多标记分析(MAGMA)基因分析中,这些变异与乳糜微粒和极低密度脂蛋白(VLDL)重塑途径有关。在两个队列中,PRS和生活方式因素之间观察到显著的相互作用,即植物性饮食(P = 0.0008)、酒精消费(P = 0.0022)和吸烟状况(P < 0.001)。此外,在KoGES队列中,维生素D摄入量(P = 0.027)和血糖指数(P = 0.045)与PRS相互作用,影响高tg风险。结论:相似的遗传变异影响人群的高tg风险,尽管风险等位基因频率存在种族差异。在两个队列中,已确定的PRS与植物性饮食、饮酒和吸烟状况显著相互作用,在韩国队列中还观察到与维生素D摄入量和血糖指数的额外相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrating genetics and lifestyles for precision nutrition in hypertriglyceridemia: A UK Biobank and KoGES analysis.

Background: Hypertriglyceridemia is an independent risk factor for cardiovascular disease.

Objective: This study examined the polygenic variants associated with high serum triglyceride concentration (high-TG) and their interactions with lifestyle factors using data from the UK Biobank (n = 479,300) and the Korean Genome and Epidemiology Study (KoGES; n = 57,939).

Methods: High-TG group was categorized based on over 200 mg/dL fasting serum TG concentrations (Caucasians, UK Biobank, n = 100,543; Koreans, KoGES, n = 7211). Polygenic risk scores (PRS) were calculated using risk alleles from genetic variants identified through a genome-wide association study (GWAS) and generalized multifactor dimensionality reduction (GMDR) analyses.

Results: Koreans showed higher frequencies of risk alleles in GCKR, APOA5, SIK3, and APOE genes compared to Caucasians. After adjusting for covariates, a PRS including lipoprotein lipase (LPL)_rs328, apolipoprotein A5 (APOA5)_rs2072560, and glucokinase regulator (GCKR)_rs780093 showed a 2.2-fold (UK Biobank) and 2.6-fold (KoGES) increased risk of high-TG among Caucasians and Koreans, respectively. In both cohorts, the PRS was positively associated with metabolic syndrome, serum low high-density lipoprotein (HDL)-cholesterol, and high low-density lipoprotein (LDL)-cholesterol concentrations, but inversely associated with high-TG. These variants were linked to the chylomicron and very low-density lipoprotein (VLDL) remodeling pathways in Multimarker Analysis of GenoMic Annotation (MAGMA) gene analysis. Significant interactions were observed between the PRS and lifestyle factors, namely plant-based diet (P = .0008), alcohol consumption (P = .0022), and smoking status (P < .001) in both cohorts. Additionally, in the KoGES cohort, vitamin D intake (P = .027) and the glycemic index (P = .045) interacted with the PRS to influence high-TG risk.

Conclusion: Similar genetic variants affected high-TG risk across populations despite ethnic differences in risk allele frequencies. The identified PRS significantly interacted with plant-based diet, alcohol consumption, and smoking status in both cohorts, with additional interactions observed with vitamin D intake and glycemic index in the Korean cohort.

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来源期刊
CiteScore
7.00
自引率
6.80%
发文量
209
审稿时长
49 days
期刊介绍: Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.
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