 |
|
Risk of Autistic Disorder in Affected Offspring of Mothers With a Glutathione S-Transferase P1 Haplotype
Tanishia A. Williams, PhD;
Audrey E. Mars, MD;
Steven G. Buyske, PhD;
Edward S. Stenroos, BS;
Rong Wang, MS;
Marivic F. Factura-Santiago, MD;
George H. Lambert, MD;
William G. Johnson, MD
Arch Pediatr Adolesc Med. 2007;161(4):356-361.
Objective To test whether polymorphisms of the glutathione S-transferase P1 gene (GSTP1) act in the mother during pregnancy to contribute to the phenotype of autistic disorder (AD) in her fetus.
Design Transmission disequilibrium testing (TDT) in case mothers and maternal grandparents.
Setting Autistic disorder may result from multiple genes and environmental factors acting during pregnancy and afterward. Teratogenic alleles act in mothers during pregnancy to contribute to neurodevelopmental disorders in their offspring; however, only a handful have been identified. GSTP1 is a candidate susceptibility gene for AD because of its tissue distribution and its role in oxidative stress, xenobiotic metabolism, and JNK regulation.
Participants We genotyped GSTP1*G313A and GSTP1*C341T polymorphisms in 137 members of 49 families with AD. All probands received a clinical diagnosis of AD by Autism Diagnostic Interview–Revised and Autism Diagnostic Observation Schedule–Generic testing.
Main Outcome Measures Association of haplotypes with AD was tested by the TDT-Phase program, using the expectation-maximization (EM) algorithm for uncertain haplotypes and for incomplete parental genotypes, with standard measures of statistical significance.
Results The GSTP1*A haplotype was overtransmitted to case mothers (P = .01 [P = .03 using permutation testing]; odds ratio, 2.67 [95% confidence interval, 1.39-5.13]). Results of the combined haplotype and genotype analyses suggest that the GSTP1-313 genotype alone determined the observed haplotype effect.
Conclusions Overtransmission of the GSTP1*A haplotype to case mothers suggests that action in the mother during pregnancy likely increases the likelihood of AD in her fetus. If this is confirmed and is a result of a gene-environment interaction occurring during pregnancy, these findings could lead to the design of strategies for prevention or treatment.
Author Affiliations: Departments of Neurology (Drs Williams and Johnson, Mr Stenroos, and Ms Wang) and Pediatrics (Drs Mars, Factura-Santiago, and Lambert) and Center for Childhood Neurotoxicology and Exposure Assessment (Drs Mars, Lambert, and Johnson), University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Piscataway, and Departments of Statistics and Genetics, Rutgers University, New Brunswick, NJ (Dr Buyske).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Looking Ahead to Even More Discoveries in Autism Spectrum Disorder While Addressing Current Needs
Schonfeld and Manning-Courtney
Arch Pediatr Adolesc Med 2007;161:412-413.
FULL TEXT
|
