脂肪酸去饱和酶基因多态性对儿童红细胞膜脂肪酸构成和认知记忆的影响
|
摘要
目的探讨脂肪酸去饱和酶(FADS)多态性对学龄儿童红细胞膜多不饱和脂肪酸(PUFAs)构成和认知记忆的影响。方法对参与补充DHA随机对照试验的8~12岁的南雄市坪田镇小学生进行基线问卷调查,收集一般情况、膳食资料、体格测量并采集空腹血。采用数字广度测试和威斯康星卡片分类测试评估认知记忆功能。测定红细胞膜脂肪酸构成,提取血凝块DNA进行FADS 4个位点的多态性分析。结果共调查106名三至五年级在校小学生,其中男生62人,女生44人,平均年龄为(9.17±1.03)岁。不同红细胞膜DHA含量构成的调查对象认知记忆功能差异无统计学意义(均P>0.05)。FADS的4个位点相互间符合H-W平衡(0.409~0.970)。FADS rs174561基因型不同C18∶2、C18∶3(n-6)、C20∶5、总n-3、AA/LA、EPA/ALA的比例差异均有统计学意义(P<0.01或P<0.05)。混合线性模型分析结果发现,完成分类数、概念化水平数、概念化水平mm+Mm基因型者高于MM基因型者(均P<0.05),mm+Mm基因型者总错误数和总错误率低于MM基因型者(均P<0.05)。结论 FADS多态性可影响学龄儿童体内PUFAs构成和认知记忆功能。
Objective To explore the effect of fatty acid desaturase(FADS) single nucleotide polymorphisms(SNPs) on erythrocyte membrane polyunsaturated fatty acids(PUFAs) composition and cognitive memory of school-age children.Methods Primary school students aged 8-12 years were selected from Pingtian Town,Nanxiong City to participate in the docosahexaenoic acid(DHA) supplementation randomized controlled trial.Basic information,dietary data,anthropometric measurements and fasting blood samples were collected.Cognitive function was assessed using digital span test and Wisconsin card sorting test.Erythrocyte membrane fatty acids composition was determined by gas chromatography.Genome DNA was extracted from blood clots and used to identify the genotypes of 4 FADS tag SNPs.Results A total of106 school students from grade three to grade five were investigated,including 62 males and 44 females,with an average age of(9.17±1.03) years.There was no significant difference in the cognitive memory function of DHA in different erythrocyte membrane(all P>0.05).The four sites of FADS were in accordance with H-W equilibrium(0.409-0.970).The differences of FADS rs174561 genotypes in different C18∶2,C18∶3(n-6),C20∶5,total n-3,AA/LA,EPA/ALA were statistically significant(P<0.01 or P<0.05).The mixed linear model analysis showed that the scores of number of completed categories and conceptual level,conceptual level for mm+Mm genotype were higher than those for MM genotype(all P<0.05).The total number of errors and total error rate of mm + Mm genotype were lower than those of MM(all P<0.05).Conclusion FADS SNPs can influence PUFAs status and cognitive function in school-age children.
Objective To explore the effect of fatty acid desaturase(FADS) single nucleotide polymorphisms(SNPs) on erythrocyte membrane polyunsaturated fatty acids(PUFAs) composition and cognitive memory of school-age children.Methods Primary school students aged 8-12 years were selected from Pingtian Town,Nanxiong City to participate in the docosahexaenoic acid(DHA) supplementation randomized controlled trial.Basic information,dietary data,anthropometric measurements and fasting blood samples were collected.Cognitive function was assessed using digital span test and Wisconsin card sorting test.Erythrocyte membrane fatty acids composition was determined by gas chromatography.Genome DNA was extracted from blood clots and used to identify the genotypes of 4 FADS tag SNPs.Results A total of106 school students from grade three to grade five were investigated,including 62 males and 44 females,with an average age of(9.17±1.03) years.There was no significant difference in the cognitive memory function of DHA in different erythrocyte membrane(all P>0.05).The four sites of FADS were in accordance with H-W equilibrium(0.409-0.970).The differences of FADS rs174561 genotypes in different C18∶2,C18∶3(n-6),C20∶5,total n-3,AA/LA,EPA/ALA were statistically significant(P<0.01 or P<0.05).The mixed linear model analysis showed that the scores of number of completed categories and conceptual level,conceptual level for mm+Mm genotype were higher than those for MM genotype(all P<0.05).The total number of errors and total error rate of mm + Mm genotype were lower than those of MM(all P<0.05).Conclusion FADS SNPs can influence PUFAs status and cognitive function in school-age children.
引文
[1]Sheppard KW,Cheatham CL.Omega-6 to omega-3 fatty acid ratio and higher-order cognitive functions in 7 to 9-y-olds:a cross-sectional study[J].Am J Clin Nutr,2013,98(3):659-667.
[2]Sorensen LB,Damsgaard CT,Dalskov SM,et al.Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children:secondary analyses of the Optimal Well-Being,Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study[J].Br J Nutr,2015,114(10):1623-1637.
[3]Montgomery P,Burton JR,Sewell RP,et al.Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior:a cross-sectional analysis from the DOLAB study[J].PLo S One,2013,8(6):e66697.
[4]Jumbe T,Comstock SS,Harris WS,et al.Whole-blood fatty acids are associated with executive function in Tanzanian children aged 4-6 years:a cross-sectional study[J].Br J Nutr,2016,116(9):1537-1545.
[5]Molto-Puigmarti C,Plat J,Mensink RP,et al.FADS1 FADS2gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk[J].Am J Clin Nutr,2010,91(5):1368-1376.
[6]Steer CD,Lattka E,Koletzko B,et al.Maternal fatty acids in pregnancy,FADS polymorphisms,and child intelligence quotient at 8 y of age[J].Am J Clin Nutr,2013,98(6):1575-1582.
[7]Harslof LB,Larsen LH,Ritz C,et al.FADS genotype and diet are important determinants of DHA status:a cross-sectional study in Danish infants[J].Am J Clin Nutr,2013,97(6):1403-1410.
[8]Jensen HA,Harslof LB,Nielsen MS,et al.FADS single-nucleotide polymorphisms are associated with behavioral outcomes in children,and the effect varies between sexes and is dependent on PPAR genotype[J].Am J Clin Nutr,2014,100(3):826-832.
[9]Koletzko B,Lattka E,Zeilinger S,et al.Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women:findings from the Avon Longitudinal Study of Parents and Children[J].Am J Clin Nutr,2011,93(1):211-219.
[10]Carter KW,Mccaskie PA,Palmer LJ.JLIN:a java based linkage disequilibrium plotter[J].BMC Bioinformatics,2006,7(1):60.
[11]Letondor A,Buaud B,Vaysse C,et al.Erythrocyte DHA level as a biomarker of DHA status in specific brain regions of n-3 longchain PUFA-supplemented aged rats[J].Br J Nutr,2014,112(11):1805-1818.
[12]Kuratko CN,Salem N.Biomarkers of DHA status[J].Prostaglandins Leukotrienes Essential Fatty Acids,2009,81(2-3):111-118.
[13]Eilander A,Muthayya S,Van Der Knaap H,et al.Undernutrition,fatty acid and micronutrient status in relation to cognitive performance in Indian school children:a cross-sectional study[J].Br J Nutr,2010,103(7):1056-1064.
[14]Glaser C,Heinrich J,Koletzko B.Role of FADS1 and FADS2polymorphisms in polyunsaturated fatty acid metabolism[J].Metabolism,2010,59(7):993-999.
[15]Rzehak P,Heinrich J,Klopp N,et al.Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2(FADS1 FADS2)gene cluster and the fatty acid composition of erythrocyte membranes[J].Br J Nutr,2009,101(1):20-26.
[16]Schaeffer L,Gohlke H,Muller M,et al.Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids[J].Hum Mol Genet,2006,15(11):1745-1756.
[17]Lupu DS,Cheatham CL,Corbin KD,et al.Genetic and epigenetic transgenerational implications related to omega-3 fatty acids.Part I:maternal FADS2 genotype and DNA methylation correlate with polyunsaturated fatty acid status in toddlers:an exploratory analysis[J].Nutr Res,2015,35(11):939-947.
[18]Cheatham CL,Lupu DS,Niculescu MD.Genetic and epigenetic transgenerational implications related to omega-3 fatty acids.Part II:maternal FADS2 rs174575 genotype and DNA methylation predict toddler cognitive performance[J].Nutr Res,2015,35(11):948-955.
[2]Sorensen LB,Damsgaard CT,Dalskov SM,et al.Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children:secondary analyses of the Optimal Well-Being,Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study[J].Br J Nutr,2015,114(10):1623-1637.
[3]Montgomery P,Burton JR,Sewell RP,et al.Low blood long chain omega-3 fatty acids in UK children are associated with poor cognitive performance and behavior:a cross-sectional analysis from the DOLAB study[J].PLo S One,2013,8(6):e66697.
[4]Jumbe T,Comstock SS,Harris WS,et al.Whole-blood fatty acids are associated with executive function in Tanzanian children aged 4-6 years:a cross-sectional study[J].Br J Nutr,2016,116(9):1537-1545.
[5]Molto-Puigmarti C,Plat J,Mensink RP,et al.FADS1 FADS2gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk[J].Am J Clin Nutr,2010,91(5):1368-1376.
[6]Steer CD,Lattka E,Koletzko B,et al.Maternal fatty acids in pregnancy,FADS polymorphisms,and child intelligence quotient at 8 y of age[J].Am J Clin Nutr,2013,98(6):1575-1582.
[7]Harslof LB,Larsen LH,Ritz C,et al.FADS genotype and diet are important determinants of DHA status:a cross-sectional study in Danish infants[J].Am J Clin Nutr,2013,97(6):1403-1410.
[8]Jensen HA,Harslof LB,Nielsen MS,et al.FADS single-nucleotide polymorphisms are associated with behavioral outcomes in children,and the effect varies between sexes and is dependent on PPAR genotype[J].Am J Clin Nutr,2014,100(3):826-832.
[9]Koletzko B,Lattka E,Zeilinger S,et al.Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women:findings from the Avon Longitudinal Study of Parents and Children[J].Am J Clin Nutr,2011,93(1):211-219.
[10]Carter KW,Mccaskie PA,Palmer LJ.JLIN:a java based linkage disequilibrium plotter[J].BMC Bioinformatics,2006,7(1):60.
[11]Letondor A,Buaud B,Vaysse C,et al.Erythrocyte DHA level as a biomarker of DHA status in specific brain regions of n-3 longchain PUFA-supplemented aged rats[J].Br J Nutr,2014,112(11):1805-1818.
[12]Kuratko CN,Salem N.Biomarkers of DHA status[J].Prostaglandins Leukotrienes Essential Fatty Acids,2009,81(2-3):111-118.
[13]Eilander A,Muthayya S,Van Der Knaap H,et al.Undernutrition,fatty acid and micronutrient status in relation to cognitive performance in Indian school children:a cross-sectional study[J].Br J Nutr,2010,103(7):1056-1064.
[14]Glaser C,Heinrich J,Koletzko B.Role of FADS1 and FADS2polymorphisms in polyunsaturated fatty acid metabolism[J].Metabolism,2010,59(7):993-999.
[15]Rzehak P,Heinrich J,Klopp N,et al.Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2(FADS1 FADS2)gene cluster and the fatty acid composition of erythrocyte membranes[J].Br J Nutr,2009,101(1):20-26.
[16]Schaeffer L,Gohlke H,Muller M,et al.Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids[J].Hum Mol Genet,2006,15(11):1745-1756.
[17]Lupu DS,Cheatham CL,Corbin KD,et al.Genetic and epigenetic transgenerational implications related to omega-3 fatty acids.Part I:maternal FADS2 genotype and DNA methylation correlate with polyunsaturated fatty acid status in toddlers:an exploratory analysis[J].Nutr Res,2015,35(11):939-947.
[18]Cheatham CL,Lupu DS,Niculescu MD.Genetic and epigenetic transgenerational implications related to omega-3 fatty acids.Part II:maternal FADS2 rs174575 genotype and DNA methylation predict toddler cognitive performance[J].Nutr Res,2015,35(11):948-955.