蛋白质和脂肪的摄入量与 PTPN11_rs11066325、RPH3A_rs886477 和 OAS3_rs2072134 的单倍型相互作用，调节中年人血清 HDL 浓度。
Protein and fat intake interacts with the haplotype of PTPN11_rs11066325, RPH3A_rs886477, and OAS3_rs2072134 to modulate serum HDL concentrations in middle-aged people.
机构信息
Dept. of Food and Nutrition, Institue of Basic Science, Obesity/Diabetes Research Center, Hoseo University, Asan, Chungnam, 31499, South Korea.
Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University, Asan, Chungnam, 31499, South Korea.
出版信息
Clin Nutr. 2020 Mar;39(3):942-949. doi: 10.1016/j.clnu.2019.03.039. Epub 2019 Apr 4.
BACKGROUND & AIMS: Low serum HDL cholesterol (HDL-C) concentration is a risk factor for cardiovascular diseases and it is influenced by genetic and environmental factors. We hypothesized that genetic variants that decrease serum HDL-C concentrations may interact with nutrient intakes in ways that increase or decrease the risk of cardiovascular disease.
METHODS
Candidate genetic variants that can lower serum HDL-C concentrations were explored by genome-wide association studies (GWAS), after adjusting for covariates, in the Ansan/Ansung cohort (n = 8842) from KoGES. The best genetic variants were selected and used to form a haplotype. According to the haplotype frequencies of SNPs, they were divided into major allele, heterozygote allele, and minor allele. The association of haplotype with serum HDL-C levels was determined using logistic regression after adjusting for confounding factors. Interaction of the haplotype with nutrient intake was also determined.
RESULTS
PTPN11_rs11066325, RPH3A_rs886477 and OAS3_rs2072134 were selected to modulate serum HDL-C levels from GWAS(P = 1.09E-09, 7.04E-10, and 1.27E-09, respectively). The adjusted odds ratios (ORs) for a decrease in serum HDL-C concentration in the minor-allele group of the haplotype were elevated by 1.534 fold, compared to the major-allele group of the haplotype. Furthermore, the adjusted ORs for serum LDL cholesterol and levels increased by 1.645 in the minor-alleles compared to the major-alleles of the haplotype without a significant change of serum cholesterol levels. Interestingly, the adjusted ORs for serum triglyceride were lower in the minor-alleles than in the major-alleles. The haplotype had a significant interaction with the intake of protein, fat, saturated fatty acids (SAF) and polyunsaturated fatty acids (PUFA; P < 0.05). In particular, the minor alleles of the haplotype decreased serum HDL-C levels compared to the major-alleles in the high intake of protein, fat, SFA, and PUFA, not in the low intake.
CONCLUSIONS
People carrying the minor-allele of haplotypes should avoid diets that are high in protein and fat, especially rich in SFA and PUFA.
背景与目的
血清高密度脂蛋白胆固醇（HDL-C）浓度低是心血管疾病的危险因素，受遗传和环境因素的影响。我们假设，降低血清 HDL-C 浓度的遗传变异可能与营养素的摄入相互作用，从而增加或降低心血管疾病的风险。
方法
通过全基因组关联研究（GWAS），在 KoGES 的 Ansan/Ansung 队列（n=8842）中，在调整协变量后，探索可能降低血清 HDL-C 浓度的候选遗传变异。选择最佳的遗传变异并形成单倍型。根据 SNP 的单倍型频率，将它们分为主要等位基因、杂合等位基因和次要等位基因。在调整混杂因素后，使用逻辑回归确定单倍型与血清 HDL-C 水平之间的关联。还确定了单倍型与营养素摄入的相互作用。
结果
从 GWAS 中选择 PTPN11_rs11066325、RPH3A_rs886477 和 OAS3_rs2072134 来调节血清 HDL-C 水平（P=1.09E-09、7.04E-10 和 1.27E-09）。与单倍型的主要等位基因组相比，单倍型的次要等位基因组中血清 HDL-C 浓度降低的调整后比值比（OR）升高了 1.534 倍。此外，与单倍型的主要等位基因相比，血清 LDL 胆固醇和水平的调整后 OR 升高了 1.645 倍，而血清胆固醇水平没有显著变化。有趣的是，单倍型的次要等位基因组中血清甘油三酯的调整后 OR 低于主要等位基因组。该单倍型与蛋白质、脂肪、饱和脂肪酸（SAF）和多不饱和脂肪酸（PUFA）的摄入有显著的交互作用（P<0.05）。特别是，与主要等位基因相比，在高蛋白质、脂肪、SAF 和 PUFA摄入的情况下，单倍型的次要等位基因降低了血清 HDL-C 水平，而在低蛋白质、脂肪、SAF 和 PUFA 摄入的情况下则没有。
结论
携带单倍型的次要等位基因的人应避免高蛋白和高脂肪饮食，特别是富含 SAF 和 PUFA 的饮食。
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