Patient-control association study of substance P-related genes in unipolar and bipolar affective disorders.
In the search of genes potentially implicated in the aetiology of affective disorders (AD), SUBSTANCE P (SP) pathway is receiving increased interest. SP receptor antagonists, such as MK-869 and L-759274, have been shown to have antidepressant effect. Results from preclinical and human studies implicate SP and its pathway in the pathophysiology of mood disorders. We investigated a possible association between 20 single nucleotide polymorphisms (SNPS) among four SP-related genes and unipolar and bipolar ad (UPAD and BPAD) in a first sample of 92 UPAD patients and 92 control individuals and in a replication sample of 92 UPAD patients and 92 control individuals. An additional sample of 113 BPAD patients has also been ascertained. Our results showed a significant association between the angiotensin-converting enzyme gene (ACE1) and UPAD in our first sample, but not in the replication sample. No significant evidence of association was found in other SP-related genes. We did not find any association in the BPAD sample. When pooling first and replication UPAD samples, an association was found between ACE1 and a subgroup of patients remaining depressed after an adequate antidepressant treatment. In conclusion, our findings do not support a major contribution of SP-related genes in UPAD and BPAD, but provides some evidence of an ace influence in treatment response to antidepressants.
Mendlewicz
Julien
J
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium. jmendlew@ulb.ac.be
Oswald
Pierre
P
Claes
Stephan
S
Massat
Isabelle
I
Souery
Daniel
D
Van Broeckhoven
Christine
C
Del-Favero
Jurgen
J
D000328:Adult; D000368:Aged; D000483:Alleles; D001530:Belgium / Q000453:epidemiology; D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013373:Substance P / Q000235:genetics*
D013373:Substance P