Two genetic variants of CD38 in subjects with autism spectrum disorder and controls.
The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p<0.040) and rs3796863 (p<0.005) showed significant associations with a subset of ASD (IQ>70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD.
Munesue
Toshio
T
Kanazawa University 21st Century Center of Excellence (COE) Program on Innovative Brain Science on Development, Learning and Memory, Kanazawa 920-8640, Japan.
Yokoyama
Shigeru
S
Nakamura
Kazuhiko
K
Anitha
Ayyappan
A
Yamada
Kazuo
K
Hayashi
Kenshi
K
Asaka
Tomoya
T
Liu
Hong-Xiang
HX
Jin
Duo
D
Koizumi
Keita
K
Islam
Mohammad Saharul
MS
Huang
Jian-Jun
JJ
Ma
Wen-Jie
WJ
Kim
Uh-Hyun
UH
Kim
Sun-Jun
SJ
Park
Keunwan
K
Kim
Dongsup
D
Kikuchi
Mitsuru
M
Ono
Yasuki
Y
Nakatani
Hideo
H
Suda
Shiro
S
Miyachi
Taishi
T
Hirai
Hirokazu
H
Salmina
Alla
A
Pichugina
Yu A
YA
Soumarokov
Andrei A
AA
Takei
Nori
N
Mori
Norio
N
Tsujii
Masatsugu
M
Sugiyama
Toshiro
T
Yagi
Kunimasa
K
Yamagishi
Masakazu
M
Sasaki
Tsukasa
T
Yamasue
Hidenori
H
Kato
Nobumasa
N
Hashimoto
Ryota
R
Taniike
Masako
M
Hayashi
Yutaka
Y
Hamada
Junichiro
J
Suzuki
Shioto
S
Ooi
Akishi
A
Noda
Mami
M
Kamiyama
Yuko
Y
Kido
Mizuho A
MA
Lopatina
Olga
O
Hashii
Minako
M
Amina
Sarwat
S
Malavasi
Fabio
F
Huang
Eric J
EJ
Zhang
Jiasheng
J
Shimizu
Nobuaki
N
Yoshikawa
Takeo
T
Matsushima
Akihiro
A
Minabe
Yoshio
Y
Higashida
Haruhiro
H
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D015331:Cohort Studies; D003431:Cross-Cultural Comparison; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D007564:Japan; D008297:Male; D008875:Middle Aged; D010121:Oxytocin / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014667:Vasopressins / Q000097:blood; D055815:Young Adult
D014667:Vasopressins; D010121:Oxytocin; D051997:ADP-ribosyl Cyclase 1