孤独症谱系障碍儿童维生素B_(12)及相关代谢产物MMA和转运蛋白TCN2的病例对照研究
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摘要
目的探讨孤独症谱系障碍(ASD)儿童体内维生素B_(12)水平,为ASD早期发现及药物治疗提供理论依据。方法收集哈尔滨市ASD儿童和正常对照儿童各89人,应用酶联免疫吸附试验技术(ELISA)测定尿液甲基丙二酸(Methylmalonic acid,MMA)及血清维生素B_(12)、转运蛋白转钴胺素蛋白Ⅱ(TranscobalaminⅡ,TCN2)的含量,应用SNaPshot对TCN2基因rs1801198位点进行基因分型。结果 ASD儿童的血清维生素B_(12)和TCN2水平[(369.08±131.88)pmol/L,(1.56±0.16)ng/mL]均低于对照组儿童[(485.16±200.33)pmol/L,(1.71±0.17)ng/mL](t值分别为-5.47,-5.92,P值均<0.05),ASD儿童尿液中MMA水平[(758.97±106.96)ng/mL]高于对照组[(693.66±121.72)ng/mL](t=3.94,P<0.05);TCN2基因rs1801198位点基因多态性与ASD的患病风险的关联无统计学意义(P值均>0.05),与血清TCN2水平的关联无统计学意义(F=1.16,P>0.05)。结论 ASD儿童维生素B_(12)潜在缺乏,应在开展ASD干预的同时加强营养干预。
Objective To investigate the level of vitamin B_(12) in children with autism spectrum disorder(ASD), and provide a theoretical basis for early detection and drug treatment of ASD. Methods A total of 89 ASD cases and 89 matched controls were collected. The levels of urinary methylmalonic acid(MMA) and serum vitamin B_(12), Transcobalamin Ⅱ(TCN2) were determined by enzyme-linked immunosorbent assay(ELISA). TCN2 gene rs1801198 was genotyped by SNaPshot. Results The serum levels of vitamin B_(12) and TCN2 in children with ASD [(369.08±131.88)pmol/L,(1.56±0.16)ng/mL] were significantly lower than those in the control group[(485.16±200.33)pmol/L,(1.71±0.17)ng/mL](t=-5.47,-5.92, P<0.05). The level of MMA in urine of ASD children [(758.97±106.96) ng/mL] was significantly higher than that in the control group[(693.66±121.72)ng/mL](t=3.94, P<0.05); The genetic polymorphism of rs1801198 locus was not associated with the risk of ASD(P>0.05), and there was no significant correlation with serum TCN2 level(F=1.16, P>0.05). Conclusion ASD children are at a potential deficiency of vitamin B_(12) and should strengthen their nutritional interventions while conducting ASD interventions.
Objective To investigate the level of vitamin B_(12) in children with autism spectrum disorder(ASD), and provide a theoretical basis for early detection and drug treatment of ASD. Methods A total of 89 ASD cases and 89 matched controls were collected. The levels of urinary methylmalonic acid(MMA) and serum vitamin B_(12), Transcobalamin Ⅱ(TCN2) were determined by enzyme-linked immunosorbent assay(ELISA). TCN2 gene rs1801198 was genotyped by SNaPshot. Results The serum levels of vitamin B_(12) and TCN2 in children with ASD [(369.08±131.88)pmol/L,(1.56±0.16)ng/mL] were significantly lower than those in the control group[(485.16±200.33)pmol/L,(1.71±0.17)ng/mL](t=-5.47,-5.92, P<0.05). The level of MMA in urine of ASD children [(758.97±106.96) ng/mL] was significantly higher than that in the control group[(693.66±121.72)ng/mL](t=3.94, P<0.05); The genetic polymorphism of rs1801198 locus was not associated with the risk of ASD(P>0.05), and there was no significant correlation with serum TCN2 level(F=1.16, P>0.05). Conclusion ASD children are at a potential deficiency of vitamin B_(12) and should strengthen their nutritional interventions while conducting ASD interventions.
引文
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[18] ZHANG Z,YU L,LI S,et al.Association study of polymorphisms in genes relevant to vitamin B12 and folate metabolism with childhood autism spectrum disorder in a han chinese population[J].Med Sci Monit,2018,24:370-376.
[2] ZABLOTSKY B,BLACK L I,MAENNER M J,et al.Estimated prevalence of autism and other developmental disabilities following questionnaire changes in the 2014 national health interview survey[J].Natl Health Stat Rep,2015(87):1-20.
[3] XU G,STRATHEARN L,LIU B,et al.Prevalence of autism spectrum disorder among us children and adolescents,2014-2016[J].JAMA,2018,319(1):81-82.
[4] ALI A,WALY M I,AL-FARSI Y M,et al.Hyperhomocysteinemia among omani autistic children:a case-control study[J].Acta Biochim Pol,2011,58(4):547-551.
[5] SCHMIDT R J,HANSEN R L,HARTIALA J,et al.Prenatal vitamins,one-carbon metabolism gene variants,and risk for autism[J].Epidemiology,2011,22(4):476-485.
[6] RAGHAVAN R,RILEY A W,VOLK H,et al.Maternal multivitamin intake,plasma folate and vitamin B12 levels and autism spectrum disorder risk in offspring[J].Paediatr Perinat Epidemiol,2018,32(1):100-111.
[7] CASTILLO-LANCELLOTTI C,MARGOZZINI P,VALDIVIA G,et al.Serum folate,vitamin B12 and cognitive impairment in Chilean older adults[J].Public Health Nutr,2015,18(14):2600-2608.
[8] LORD C,RISI S,LAMBRECHT L,et al.The autism diagnostic observation schedule-generic:a standard measure of social and communication deficits associated with the spectrum of autism[J].J Autism Dev Disord,2000,30(3):205-223.
[9] DE BILDT A,OOSTERLING I J,VAN LANG N D,et al.How to use the ADI-R for classifying autism spectrum disorders?Psychometric properties of criteria from the literature in 1,204 Dutch children[J].J Autism Dev Disord,2013,43(10):2280-2294.
[10] JASIEN J M,BONNER M,D’ ALLI R,et al.Cognitive,adaptive,and behavioral profiles and management of alternating hemiplegia of childhood[J].Dev Med Child Neurol,2018.DOI:10.1111/dmcn.14077.
[11] AL-FARSI Y M,WALY M I,DETH R C,et al.Low folate and vitamin B12 nourishment is common in omani children with newly diagnosed autism[J].Nutrition,2013,29(3):537-541.
[12] 孙彩虹,李楠楠,赵栋,等.孤独症儿童膳食及营养状况的对比研究[J].中国儿童保健杂志,2013,21(6):581-583.
[13] LANGAN R C,GOODBRED A J.Vitamin B12 deficiency recognition and management[J].Am Fm Physician,2017,96(6):384-389.
[14] BOUSSELAMTI A,EL HASBAOUI B,ECHAHDI H,et al.Psychomotor regression due to vitamin B12 deficiency[J].Pan Afr Med J,2018,30:152.DOI:10.11604/pamj.2018.30.152.12046.
[15] OUSSALAH A,LEVY J,FILHINE-TRESARRIEU P,et al.Association of TCN2 rs1801198 c.776G>C polymorphism with markers of one-carbon metabolism and related diseases:a systematic review and meta-analysis of genetic association studies[J].Am J Clin Nutr,2017,106(4):1142-1156.
[16] MITCHELL E S,CONUS N,KAPUT J.B vitamin polymorphisms and behavior:evidence of associations with neurodevelopment,depression,schizophrenia,bipolar disorder and cognitive decline[J].Neurosci Biobehav Rev,2014,47:307-320.DOI:10.1016/j.nevbiorev.2014.08.006.
[17] HAGHIRI R,MASHAYEKHI F,BIDABADI E,et al.Analysis of methionine synthase (rs1805087) gene polymorphism in autism patients in Northern Iran[J].Acta Neurobiol Exp(Wars),2016,76(4):318-323.
[18] ZHANG Z,YU L,LI S,et al.Association study of polymorphisms in genes relevant to vitamin B12 and folate metabolism with childhood autism spectrum disorder in a han chinese population[J].Med Sci Monit,2018,24:370-376.