A NOS-III haplotype that includes functional polymorphisms is associated with bipolar disorder.
The pleiotropic messenger molecule nitric oxide (NO) has been implicated in a variety of higher CNS functions, including learning, memory, and emotionality. In the human brain, NO is predominantly formed by neuronal NO synthase (NOS-I), while the so-called 'endothelial' isoform NOS-III also contributes to NO generation. We recently reported that NOS-III knockout mice display decreased adult neurogenesis and reduced responsiveness in a learned helplessness paradigm. To examine whether NOS-III plays a role in affective disorders as well, we tested a NOS-III gene haplotype, consisting of three functional polymorphisms, for an association with bipolar disorder and major depression. A significant global haplotype association with bipolar disorder (n = 284 controls; n = 91 patients; p(global) = 0.021; p(t-a-g) < 0.001), but not unipolar depression (n = 45) was detected. Our results thus suggest that the NOS-III genotype may convey a modest genetic risk to develop bipolar disorder. This finding should be further clarified by the use of within-family designs and in samples of other ethnicity.
Reif
Andreas
A
Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany. a.reif@gmx.net
Strobel
Alexander
A
Jacob
Christian P
CP
Herterich
Sabine
S
Freitag
Christine M
CM
Töpner
Theresia
T
Mössner
Rainald
R
Fritzen
Sabrina
S
Schmitt
Angelika
A
Lesch
Klaus-Peter
KP
D000328:Adult; D001714:Bipolar Disorder / Q000209:etiology / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III