Source: Psychiatry Source

Date: November 16 2007

Cannabis and smoking gene links to schizophrenia unfounded

MedWire News: Schizophrenia risk is not influenced by variations in the
cannabinoid receptor (CNR1) and alpha7-nicotinic acetylcholine receptor
(CHRNA7) genes, say UK researchers.

They also found no evidence for the purported effects of cannabis use on
schizophrenia according to variation in the catechol-O-methyltransferase
(COMT) gene.

Schizophrenia is associated with an increased use of tobacco and
cannabis, with evidence suggesting that patients may use the drug to
alleviate neurophysiological symptoms. The benefits of these substances
are thought to be mediated through their effects on CHRNA7 and CNR1,
respectively, notes the team.

They therefore looked at the effects of variants in the genes encoding
CHRNA7 and CNR1 on the risk for schizophrenia and the potential effects
of tobacco and cannabis use.

Stanley Zammit, from Cardiff University, and colleagues genotyped 750
patients with schizophrenia and 688 mentally healthy controls for the
CHRNA7 promoter polymorphism -86C/T and the CNR1 polymorphism rs1049353.
They also gathered information on tobacco and cannabis use via
interviews and case-note records.

In addition, the team conducted a case-only study of 493 participants
from the schizophrenia group, examining interactions between cannabis
use and the Val158Met polymorphism in the COMT gene, as well as the
rs737865 and rs165599 single nucleotide polymorphisms (SNPs).

The team reports in the British Journal of Psychiatry that there was no
evidence of an association between the CHRNA7 -86C/T genotype and
schizophrenia. Schizophrenia patients were 4.4 times more likely than
controls to smoke, but among the schizophrenia patients, there was no
association between tobacco use and the -86C/T genotype.

Similarly, there was no significant association between the CNR1
rs1049353 genotype and schizophrenia. Schizophrenia patients were 2.6
times more likely than controls to use cannabis, but cannabis use was
not affected by rs1049353 genotype among schizophrenia patients.

The results also showed that there were no associations between the
Val158Met genotype and cannabis use, or between cannabis use and the
variations at rs737865 and rs165599.

The only genetic effect on phenotypes of schizophrenia was a weak
association between the -86C/T genotype and a younger age at onset of
schizophrenia.

“In summary, we failed to find any evidence that variation at the CHRNA7
or CNR1 locus was associated with schizophrenia, or that the effect of
variation at these loci was modified by use of tobacco or cannabis,
respectively,” the researchers write.

They add: “Cannabis use was not associated with the presence of valine
allele at Val158Met with COMT in our sample, therefore our findings do
not support a previous report of a putative gene–environment interaction
between COMT genotype and cannabis use on risk of schizophrenia.”

Source: Br J Psychiatry 2007; 191: 402–407

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