NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids
NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids
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DOI：
10.1016/j.atherosclerosis.2010.03.027
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发表时间：
2010-08-01
期刊：
影响因子：
5.3
通讯作者：
Roche, Helen M.
中科院分区：
文献类型：
--
作者：
Ferguson, Jane F.;Phillips, Catherine M.;Roche, Helen M.
目的：研究ω-3多不饱和脂肪酸（n-3 PUFA）对心血管疾病的预防作用.关键基因如一氧化氮合酶（NOS 3）的基因型可能决定对脂肪酸的反应。基因-营养素相互作用在调节CVD的发展中可能是重要的，特别是在患有代谢综合征（MetS）的高危个体中。CVD风险的生物标志物、血浆脂肪酸组成和NOS 3单核苷酸多态性（SNP）基因型（rs 11771443、rs 1800783、rs 1800779、rs 1799983、rs3918227和rs743507）。饮食脂肪修饰12周的代谢指标的MetS的影响进行了测定，以了解潜在的NOS 3基因-营养interactions.Results：几个标志物的炎症和血脂异常的基因型组之间有显着差异。NOS 3 rs 1799983 SNP和血浆n-3 PUFA状态对血浆三酰甘油（TAG）浓度的影响存在显著的基因-营养素相互作用。次要等位基因携带者（AC + AA）与低血浆n-3 PUFA状态的患者血浆TAG浓度显著升高呈负相关，反之亦然，但主要等位基因纯合子（CC）则无此相关性。补充n-3多不饱和脂肪酸后，血浆TAG浓度的次要等位基因携带者的rs 1799983的血浆n-3多不饱和脂肪酸的变化，比主要等位基因纯合子。结论：携带者的次要等位基因的rs 1799983在NOS 3的血浆TAG浓度更响应于n-3多不饱和脂肪酸。这表明这些个体可能显示出n-3 PUFA消耗对降低血浆TAG浓度的更大有益作用。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Objective: Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene-nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS).Methods: Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene-nutrient interactions.Results: Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene-nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC + AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes.Conclusions: Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations. (C) 2010 Elsevier Ireland Ltd. All rights reserved.