FADS1、FADS2基因多态性与中国汉族孤独症谱系障碍的关联研究
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摘要
目的分析参与多不饱和脂肪酸代谢的FADS1和FADS2基因单核苷酸多态性(SNPs)与中国汉族孤独症谱系障碍(ASD)患儿的相关性。方法采用病例对照的研究方法,收集病例和对照各243例,采集外周血并提取DNA。利用人类基因库数据和Haploview 4.2软件筛选FADS1和FADS2基因的标签SNPs,采用Sequenom Mass ARRAY系统对SNPs进行基因分型,采用Logistic回归分析标签SNPs与ASD发病风险之间的关联。结果病例组和对照组儿童FADS2基因的rs526126等位基因频率和基因型频率差异有统计学意义[G等位基因OR=0.54(0.41~0.72),G/G基因型OR=0.05(0.02~0.19),P均<0.001]。结论 FADS2基因可能与中国汉族儿童ASD发病风险存在关联性。
Objective To analyze whether single nucleotide polymorphisms(SNPs)in FADS1 and FADS2 genes involved in polyunsaturated fatty acids metabolism are related to the risk of autism spectrum disorder(ASD)among Chinese population.Methods A total of 243 subjects with ASD and 243 control subjects were enrolled in this case-control study.Genomic DNA was extracted from peripheral whole blood samples.The human genome database and the Haploview 4.2 software were used to select tag SNPs.All tag SNPs genotyping were set by using the Sequenom Mass ARRAY.Associations between the tag SNPs and ASD were analyzed by logistic regression analysis.Results The allele and genotype frequencies at rs526126 in FADS2 showed significant differences between autistic children and control group[rs526126 Gallele OR=0.54(0.41~0.72),P<0.001,G/G genotype OR=0.05(0.02~0.18),P<0.001].Conclusion This study provides supportive evidence on association of the polymorphisms in FADS2 gene with ASD risk in Chinese Han nationality population.
Objective To analyze whether single nucleotide polymorphisms(SNPs)in FADS1 and FADS2 genes involved in polyunsaturated fatty acids metabolism are related to the risk of autism spectrum disorder(ASD)among Chinese population.Methods A total of 243 subjects with ASD and 243 control subjects were enrolled in this case-control study.Genomic DNA was extracted from peripheral whole blood samples.The human genome database and the Haploview 4.2 software were used to select tag SNPs.All tag SNPs genotyping were set by using the Sequenom Mass ARRAY.Associations between the tag SNPs and ASD were analyzed by logistic regression analysis.Results The allele and genotype frequencies at rs526126 in FADS2 showed significant differences between autistic children and control group[rs526126 Gallele OR=0.54(0.41~0.72),P<0.001,G/G genotype OR=0.05(0.02~0.18),P<0.001].Conclusion This study provides supportive evidence on association of the polymorphisms in FADS2 gene with ASD risk in Chinese Han nationality population.
引文
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[17]Tosi F,Sartori F,Guarini P,et al.Delta-5and delta-6desaturases:crucial enzymes in polyunsaturated fatty acid-related pathways with pleiotropic influences in health and disease[J].Adv Exp Med Biol,2014,824:61-81.
[18]Young AMH,Chakrabarti B,Roberts D,et al.From molecules to neural morphology:understanding neuroinflammation in autism spectrum condition[J].Mol Autism,2016,7(1):1-8.
[2]Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008Principal Investigators.Prevalence of autism spectrum disorders-autism and developmental disabilities monitoring network,14sites,united states,2008[J].MMWR Surveill Summ,2012,61(3):1-19.
[3]Autism and Developmental Disabilities Monitoring Network Surveillance Year 2010Principal Investigators.Prevalence of autism spectrum disorder among children aged 8years-autism and developmental disabilities monitoring network,11sites,united states,2010[J].MMWR Surveill Summ,2014,63(2):1-21.
[4]Jory J.Abnormal fatty acids in Canadian children with autism[J].Nutrition,2015,32(4):474-477.
[5]武丽杰.多不饱和脂肪酸与孤独症发病关联的研究进展[J].中国儿童保健杂志,2013,21(6):565-566.
[6]Guha M.Diagnostic and Statistical Manual of Mental Disorders:DSM-5(5th edition)[J].Reference Reviews,2014,28(3):36-37.
[7]庞伟,康倩倩,郭岚敏,等.孤独症儿童血浆多不饱和脂肪酸水平研究[J].中国康复理论与实践,2011,17(8):742-744.
[8]Drumond A,Madeira N,Fonseca R.Endocannabinoid signaling and memory dynamics:a synaptic perspective[J].Neurobiol Learn Mem,2017,138:62-77.
[9]Joffre C,Nadjar A,Lebbadi M,et al.n-3LCPUFA improves cognition:the young,the old and the sick[J].Prostaglandins Leukot Essent Fatty Acids,2014,91(1-2):1-20.
[10]McNamara RK,Strawn JR.Role of long-chain Omega-3fatty acids in psychiatric practice[J].Pharma Nutrition,2013,1(2):41-49.
[11]Bousquet M,Gue K,Emond V,et al.Transgenic conversion of omega-6into omega-3fatty acids in a mouse model of Parkinson's disease[J].J Lipid Res,2011,52(2):263-271.
[12]Schuchardt JP,Kobe T,Witte V,et al.Genetic variants of the FADS gene cluster are associated with erythrocyte membrane LC PUFA levels in patients with mild cognitive impairment[J].J Nutr Health Aging,2016,20(6):611-620.
[13]孙蒙,王涵,王茂清,等.利用UPLC/Q-TOF MSMS对孤独症患儿血清的代谢组学分析[J].中国儿童保健杂志,2013,21(1):6-9.
[14]Gang Z,Gao J,Shuang L,et al.Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate-induced autism model[J].Int J Dev Neurosci,2015,44:14-21.
[15]Roke K,Ralston JC,Abdelmagid S,et al.Variation in the FADS1/2gene cluster alters plasma n-6 PUFA and is weakly associated with hsCRP levels in healthy young adults[J].Prostaglandins Leukot Essent Fatty Acids,2013,89(4):257-263.
[16]Morales E,Bustamante M,Gonzalez JR,et al.Genetic variants of the FADS gene cluster and ELOVL gene family,colostrums LC-PUFA levels,breastfeeding,and child cognition[J].PLoS One,2011,6(2):e17181.
[17]Tosi F,Sartori F,Guarini P,et al.Delta-5and delta-6desaturases:crucial enzymes in polyunsaturated fatty acid-related pathways with pleiotropic influences in health and disease[J].Adv Exp Med Biol,2014,824:61-81.
[18]Young AMH,Chakrabarti B,Roberts D,et al.From molecules to neural morphology:understanding neuroinflammation in autism spectrum condition[J].Mol Autism,2016,7(1):1-8.