International Meeting for Autism Research (London, May 15-17, 2008): The Association of a MET Promoter Variant with Autism is Dependent on Disease Classification

Thursday, May 15, 2008

Champagne Terrace/Bordeaux (Novotel London West)

11:30 AM

P. B. Jackson , JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC

L. Boccuto , Institute of Medical Genetics, Catholic University, Rome, Italy

C. Skinner , JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC

J. S. Collins , JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC

R. E. Stevenson , JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC

G. Neri , Institute of Medical Genetics, Catholic University, Rome, Italy

F. Gurrieri , Institute of Medical Genetics, Catholic University, Rome, Italy

C. E. Schwartz , JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC

Background: A 2006 report by Campbell et al. (PNAS) showed that a variant in the promoter region of the MET gene (rs1858830) on chromosome 7q31 was associated with autism.

Objectives: To replicate previous findings using South Carolina and Italian autism cohorts.

Methods: Analyses were performed using samples from 270 autism patients and 460 controls. Fifty-six patients with autism spectrum disorder (ASD) were from Italy and 162 patients with classical autism were from the South Carolina Autism Project (Schroer et al. 1998 Am J Med Genet). Control samples consisted of 91 individuals from Italy and 369 from South Carolina. The rs1858830 variant was genotyped by PCR amplification and Eag I digestion. Fragments were separated and scored using agarose gel electrophoresis.

Results: Italian and South Carolina patient and control populations were found to be in Hardy-Weinberg equilibrium. In the Italian cohort, no significant association with ASD was found when comparing the CC to the GG genotype (odds ratio = 1.12; 95% CI = 0.47-2.67). Chi-square tests similar to those performed by Campbell et al. were not found to be significant.

In the South Carolina cohort, a significant association with classical autism was found when comparing the CC to the GG genotype (odds ratio = 1.89; 95% CI = 1.08-3.31). This association was also significant for cases from simplex families (odds ratio = 2.03; 95% CI = 1.14-3.61). Chi-square tests similar to those performed by Campbell et al. were found to be significant.

Conclusions: The rs1858830 variant was not found to be associated with ASD in an Italian cohort. However, this variant was found to be associated with classical autism in a South Carolina cohort. Since Campbell et al. found a stronger association in families with narrowly defined autism, these results imply that the MET promoter variant is more strongly associated with classical autism than ASD.

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