中科院上海生科院营养所在多不饱和脂肪酸遗传易感基因研究获进展
中科院上海生科院营养所林旭研究组,在开展亚洲人群多不饱和脂肪酸遗传易感基因研究中获新发现。相关研究成果日前在线发表于《人类分子遗传学》。


国际遗传学期刊Human Molecular Genetics(《人类分子遗传学》)近日在线发表了中国科学院上海生命科学研究院营养科学研究所林旭研究组开展亚洲人群多不饱和脂肪酸全基因组关联研究的成果:Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations,文章报道了多不饱和脂肪酸遗传易感基因研究的新发现。

最近由美国农业部和健康人类服务部共同发布的最新版《美国膳食指南科学报告》中,取消了脂肪占总膳食摄入能量30%的比例,由于与以往一直提倡的“低脂膳食”的观点大相径庭,从而引起了国内外的广泛关注。除此之外,该报告还强调了优化膳食脂肪种类,推荐富含不饱和脂肪酸的植物油如大豆油、玉米油、橄榄油和菜油等作为膳食脂肪的主要来源。然而由于中西方人群在饮食习惯和遗传背景方面的差异,有关多不饱和脂肪酸全基因组关联迄今为止仅在西方人群中开展过两项研究。因此,美国健康膳食建议在多大程度上能有助于我国居民的健康仍有待研究。

在该研究中,林旭组的博士研究生胡瑶、研究员黎怀星等人通过整合1万2千多例的人群全基因组关联研究数据以及该团队建立的亚洲最大的脂肪酸谱数据库信息,结合与西方人群联盟CHARGE合作开展跨种族多不饱和脂肪酸荟萃分析研究,主要发现包括:1) 首次在中国人群中发现了与n-6多不饱和脂肪酸二十二碳四烯酸(22:4n-6, DTA)水平显著相关的两个新的遗传位点MYB-rs9399137和AGPAT4-rs729986,并且这两个位点在中西方人群间存在显著的异质性;2) 通过跨种族荟萃分析发现两个新的位点中携带rs10899123-C等位基因的人群n-6多不饱和脂肪酸γ-亚麻酸(18:3n-6, GLA)水平显著升高,而携带rs3134603-A等位基因的人群n-3多不饱和脂肪酸二十二碳五烯酸(22:5n-3, DPA)水平显著增加;3) 在中国人群中验证了5个西方人群中曾报道过的位点,同时还发现中西方人群在脂肪酸去饱和酶1基因(FADS1)位点对相关多不饱和脂肪酸水平影响的效应方面存在差异。此外,还在脂肪酸延长酶2基因(ELOVL2)上发现了独立于西方人群的位点。

该研究不仅为今后多不饱和脂肪酸相关的基因结构、基因功能、相关机理和跨种族研究提供了重要线索,同时也为将来制定适合中国人群营养推荐和“精准营养”的开展提供了循证依据。

该工作获得了科技部“973”计划、自然科学基金和面上项目等科研基金的资助。

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  • Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations

    Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor)≥6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor)=11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P=4.15×10−14 and 4.30×10−12, respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor)=6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor)=6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P≤0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.

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