Polymorphisms differ from mutations in that mutations are episodic while polymorphisms are population variations — ancient mutations that have established themselves within an observable segment of a population.

Promoters, those regions upstream of a gene, can control how much of a gene is expressed (“gene dosage”) and under what conditions that gene is expressed, all of which can vary from cell to cell.

The summed effects of polymorphisms, including those found in promoters, may be important factors at the heart of predisposing conditions for complex diseases.

Recently, papers have been published which implicate promoter polymorphisms for several complex and acute diseases, including RA, diabetes, sepsis, atherosclerosis, and depression.

On the 19th of October 2006, a group at Vanderbilt (Campbell et al) have found a p=0.0005 association with promoter variants of MET receptor tyrosine kinase, which significance rises to p=0.000007 in families with more than one autistic child. The data implicate reduced MET gene expression in autism. The researchers pegged MET partly by their observations that MET might be associated with the observed gastrointestinal and immune symptoms that are often reported to accompany autism.

It is significant for its direct genetic link to autism across multiple families.

The polymorphism is also interesting in that it seems to confer a 2x decreased MET promoter activity.

Citation:

Daniel B. Campbell, James S. Sutcliffe, Philip J. Ebert, Roberto Militerni, Carmela Bravaccio, Simona Trillo, Maurizio Elia, Cindy Schneider, Raun Melmed, Roberto Sacco, Antonio M. Persico, and Pat Levitt. “A genetic variant that disrupts MET transcription is associated with autism”. PNAS published October 19, 2006.

http://www.pnas.org/cgi/content/abstract/0605296103v1