Association of neural cell adhesion molecule 1 gene polymorphisms with bipolar affective disorder in Japanese individuals.
BACKGROUND
Although the pathogenesis of mood disorders remains unclear, heritable factors have been shown to be involved. Neural cell adhesion molecule 1 (NCAM1) is known to play important roles in cell migration, neurite growth, axonal guidance, and synaptic plasticity. Disturbance of these neurodevelopmental processes is proposed as one etiology for mood disorder. We therefore undertook genetic analysis of NCAM1 in mood disorders.


METHODS
We determined the complete genomic organization of human NCAM1 gene by comparing complementary deoxyribonucleic acid and genomic sequences; mutation screening detected 11 polymorphisms. The genotypic, allelic, and haplotype distributions of these variants were analyzed in unrelated control individuals (n = 357) and patients with bipolar disorder (n = 151) and unipolar disorder (n = 78), all from central Japan.


RESULTS
Three single nucleotide polymorphisms, IVS6+32T>C, IVS7+11G>C and IVS12+21C>A, displayed significant associations with bipolar disorder (for allelic associations, nominal p =.04, p =.02, and p =.004, respectively, all p >.05 after Bonferroni corrections). Furthermore, the haplotype located in a linkage disequilibrium block was strongly associated with bipolar disorder (the p value of the most significant three-marker haplotype is .005).


CONCLUSIONS
Our results suggest that genetic variations in NCAM1 or nearby genes could confer risks associated with bipolar affective disorder in Japanese individuals.
Arai
Makoto
M
Department of Schizophrenia Research, Tokyo Metropolitan Organization for Medical Research, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Itokawa
Masanari
M
Yamada
Kazuo
K
Toyota
Tomoko
T
Arai
Mayumi
M
Haga
Seiichi
S
Ujike
Hiroshi
H
Sora
Ichiro
I
Ikeda
Kazuhiko
K
Yoshikawa
Takeo
T
D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic
D019006:Neural Cell Adhesion Molecules