载脂蛋白中的单核苷酸多态性导致美国健康成年人在高脂饮食挑战前后血脂出现性别差异。
SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults.
作者信息
Wang Yining E, Kirschke Catherine P, Woodhouse Leslie R, Bonnel Ellen L, Stephensen Charles B, Bennett Brian J, Newman John W, Keim Nancy L, Huang Liping
机构信息
Integrative Genetics and Genomics, University of California at Davis, One Shields Ave, Davis, CA, 95616, USA.
USDA/ARS/Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA, 95616, USA.
出版信息
BMC Nutr. 2022 Sep 1;8(1):95. doi: 10.1186/s40795-022-00592-x.
BACKGROUND
The effect of genetic polymorphisms on fasting blood lipid levels have been widely studied but the effects of these within the context of a high-fat meal challenge remain less characterized. The current study aimed to investigate the association of SNPs in lipoprotein-related genes with blood lipid profiles in healthy adults in the U.S.
METHODS
Subjects (n = 393) between 18-66 years of age with BMIs ranging from 18.5-45 kg/m were enrolled the cross-sectional Nutritional Phenotyping Study. Among them, 349 subjects (men: 48%; women: 52%) gave consent for genotyping. SNPs in APOA5, APOB, APOC3, APOE, and LDLR were assessed. The association between lipid markers and genotypes was tested separately for each SNP with analysis of variance (ANOVA), adjusted for sex, age, and BMI. We also examined two-factor interactions between SNPs and sex, age, or BMI.
RESULTS
Women carrying the C allele of rs3135506 in APOA5 or men carrying the C allele of rs429358 in APOE had reduced HDL-cholesterol levels during fasting and postprandially. The C allele in APOE was also correlated to increased LDL-C levels. The TT genotype of rs2854116 in APOC3 was associated with elevated total cholesterol. Additive effect of the risk alleles of APOA5 and APOE or APOC3 and APOE was detected. Nevertheless, the tested SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. We found no significant effects of SNPs in APOB (rs1042034) or LDLR (rs2228671) on triglycerides, cholesterol, or free fatty acid levels.
CONCLUSIONS
In healthy adults, fasting and postprandial cholesterol levels are strongly correlated with the tested APOA5, APOE, and APOC3 genotypes. Sex contributes to the genetic impact of the tested SNPs on lipid profiles.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02367287. Registered February 20, 2015, https://clinicaltrials.gov/ct2/show/NCT02367287 .
背景
基因多态性对空腹血脂水平的影响已得到广泛研究，但在高脂餐挑战背景下这些影响的特征仍不太明确。本研究旨在调查美国健康成年人脂蛋白相关基因单核苷酸多态性（SNP）与血脂谱之间的关联。
方法
将年龄在18 - 66岁、体重指数（BMI）范围为18.5 - 45kg/m²的受试者纳入横断面营养表型研究（n = 393）。其中，349名受试者（男性：48%；女性：52%）同意进行基因分型。评估了载脂蛋白A5（APOA5）、载脂蛋白B（APOB）、载脂蛋白C3（APOC3）、载脂蛋白E（APOE）和低密度脂蛋白受体（LDLR）中的SNP。对每个SNP分别用方差分析（ANOVA）测试脂质标志物与基因型之间的关联，并对性别、年龄和BMI进行校正。我们还研究了SNP与性别、年龄或BMI之间的双因素相互作用。
结果
携带APOA5中rs3135506的C等位基因的女性或携带APOE中rs429358的C等位基因的男性在空腹和餐后的高密度脂蛋白胆固醇（HDL - 胆固醇）水平降低。APOE中的C等位基因也与低密度脂蛋白胆固醇（LDL - C）水平升高相关。APOC3中rs2854116的TT基因型与总胆固醇升高有关。检测到APOA5和APOE或APOC3和APOE风险等位基因的加性效应。然而，所测试的SNP对高脂挑战餐后的餐后甘油三酯反应影响很小。我们发现APOB（rs1042034）或LDLR（rs2228671）中的SNP对甘油三酯、胆固醇或游离脂肪酸水平没有显著影响。
结论
在健康成年人中，空腹和餐后胆固醇水平与所测试的APOA5、APOE和APOC3基因型密切相关。性别对所测试的SNP对血脂谱的遗传影响有作用。
试验注册
ClinicalTrials.gov，NCT02367287。于2015年2月20日注册，https://clinicaltrials.gov/ct2/show/NCT02367287 。
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