Monoallelic and unequal allelic expression of the HTR2A gene in human brain and peripheral lymphocytes.
BACKGROUND
The 102T/C polymorphism of the serotonin 2A receptor (HTR2A) gene is reported to be associated with schizophrenia and other diseases and phenotypes. Altered HTR2A expression has been found in relation to several neuropsychiatric conditions, including depression and schizophrenia. Studies of expression of HTR2A messenger RNA (mRNA) and protein in postmortem brains suggest that the 102C allele might be less transcriptionally active than the T allele. However, equal expression of both alleles has also been reported.


METHODS
We performed primer extension assays to measure relative expression of allele-specific HTR2A transcripts in mRNAs isolated from the prefrontal cortex of 31 individuals with schizophrenia and from peripheral lymphocytes (PBLs) of 31 healthy individuals heterozygous for 102T/C. We also examined the allele transmission pattern of HTR2A in PBLs of nine families.


RESULTS
Analyses of DNA and mRNA revealed that 102C is expressed but at lower levels than 102T in brains. In contrast to the biallelic expression observed in brains, monoallelic expression of HTR2A was common in PBLs. However, a family study revealed that imprinting was not responsible for the monoallelic expression in PBLs.


CONCLUSIONS
The present study revealed a tissue-specific modification of HTR2A expression, which makes allelic and epiallelic analyses necessary for genetic epidemiologic and pharmacogenomic studies of HTR2A.
Fukuda
Yoshiko
Y
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Koga
Minori
M
Arai
Makoto
M
Noguchi
Emiko
E
Ohtsuki
Tsuyuka
T
Horiuchi
Yasue
Y
Ishiguro
Hiroki
H
Niizato
Kazuhiro
K
Iritani
Shyuji
S
Itokawa
Masanari
M
Arinami
Tadao
T
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001923:Brain Chemistry / Q000235:genetics*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A