Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression.
BACKGROUND
Genetic variations in the serotonin receptor 3A (HTR3A) and 3B (HTR3B) genes, positioned in tandem on chromosome 11q23.2, have been shown to be associated with psychiatric disorders in samples of European ancestry. But the polymorphisms highlighted in these reports map to different locations in the two genes, therefore it is unclear which gene exerts a stronger effect on susceptibility.


METHODS
To determine the haplotype block structure in the genomic regions of HTR3A and HTR3B, and to examine whether genetic variations in the region show evidence of association with schizophrenia and affective disorder in the Japanese, we performed haplotype-based case-control analysis using 29 polymorphisms.


RESULTS
Two haplotype blocks each were revealed for HTR3A and HTR3B in Japanese samples. In HTR3B, haplotype block 2 that included a nonsynonymous single nucleotide polymorphism (SNP), yielded evidence of association with major depression in females (global p = .0023). Analysis employing genome-wide SNPs using the STRUCTURE program did not detect population stratification in the samples.


CONCLUSIONS
Our results suggest an important role for HTR3B in major depression in women and also raise the possibility that previously proposed disease-associated SNPs in the HTR3A/B region in Caucasians are in linkage disequilibrium with haplotype block 2 of HTR3B in the Japanese.
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Kawaguchi, Saitama, Japan.
Kazuo
K
Yamada
Eiji
E
Hattori
Yoshimi
Y
Iwayama
Tetsuo
T
Ohnishi
Hisako
H
Ohba
Tomoko
T
Toyota
Hitomi
H
Takao
Yoshio
Y
Minabe
Noriaki
N
Nakatani
Teruhiko
T
Higuchi
Sevilla D
SD
Detera-Wadleigh
Takeo
T
Yoshikawa
D000328:Adult; D030541:Databases, Genetic; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000453:epidemiology / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics
D044406:Receptors, Serotonin, 5-HT3