Population- and family-based studies associate the MTHFR gene with idiopathic autism in simplex families.
Two methylenetetrahydrofolate reductase gene (MTHFR) functional polymorphisms were studied in 205 North American simplex (SPX) and 307 multiplex (MPX) families having one or more children with an autism spectrum disorder. Case-control comparisons revealed a significantly higher frequency of the low-activity 677T allele, higher prevalence of the 677TT genotype and higher frequencies of the 677T-1298A haplotype and double homozygous 677TT/1298AA genotype in affected individuals relative to controls. Family-based association testing demonstrated significant preferential transmission of the 677T and 1298A alleles and the 677T-1298A haplotype to affected offspring. The results were not replicated in MPX families. The results associate the MTHFR gene with autism in SPX families only, suggesting that reduced MTHFR activity is a risk factor for autism in these families.
Department of Psychiatry & Physiology, Queen's University, Autism Research Program, Ongwanada Resource Centre, 191 Portsmouth Avenue, Kingston, ON K7M 8A6, Canada.
Xudong
X
Liu
Fatima
F
Solehdin
Ira L
IL
Cohen
Maripaz G
MG
Gonzalez
Edmund C
EC
Jenkins
M E Suzanne
ME
Lewis
Jeanette J A
JJ
Holden
D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D042965:Methylenetetrahydrofolate Reductase (NADPH2)