Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

被引：150

作者：

Munesue, Toshio ^{[2
,3
,4
,6
,10
,11
]}

Yokoyama, Shigeru ^{[1
,2
,10
]}

Nakamura, Kazuhiko ^{[12
]}

Anitha, Ayyappan ^{[12
]}

Yamada, Kazuo ^{[13
]}

Hayashi, Kenshi ^{[1
,5
,7
]}

Asaka, Tomoya ^{[14
]}

Liu, Hong-Xiang ^{[1
,2
]}

Jin, Duo ^{[1
,2
]}

Koizumi, Keita ^{[1
,2
,3
,11
]}

Islam, Mohammad Saharul ^{[1
,2
,10
]}

Huang, Jian-Jun ^{[1
,2
]}

Ma, Wen-Jie ^{[1
,2
,10
]}

Kim, Uh-Hyun ^{[15
]}

Kim, Sun-Jun ^{[16
]}

Park, Keunwan ^{[17
]}

Kim, Dongsup ^{[17
]}

Kikuchi, Mitsuru ^{[4
,6
,18
]}

Ono, Yasuki ^{[6
]}

Nakatani, Hideo ^{[6
]}

Suda, Shiro ^{[12
]}

Miyachi, Taishi ^{[12
]}

Hirai, Hirokazu ^{[2
,19
]}

Salmina, Alla ^{[20
]}

Pichugina, Yu A. ^{[1
,21
]}

Soumarokov, Andrei A. ^{[21
]}

Takei, Nori ^{[11
,12
,22
]}

Mori, Norio ^{[11
,12
,22
]}

Tsujii, Masatsugu ^{[11
,23
]}

Sugiyama, Toshiro ^{[2
,24
]}

Yagi, Kunimasa ^{[7
]}

Yamagishi, Masakazu ^{[7
]}

Sasaki, Tsukasa ^{[25
,26
]}

Yamasue, Hidenori ^{[10
,26
]}

Kato, Nobumasa ^{[10
,26
,27
]}

Hashimoto, Ryota ^{[11
,28
]}

Taniike, Masako ^{[11
,28
]}

Hayashi, Yutaka ^{[8
]}

Hamada, Junichiro ^{[8
]}

Suzuki, Shioto ^{[9
]}

Ooi, Akishi ^{[9
]}

Noda, Mami ^{[29
]}

Kamiyama, Yuko ^{[29
]}

Kido, Mizuho A. ^{[30
]}

Lopatina, Olga ^{[1
,2
,10
,20
]}

Hashii, Minako ^{[1
,10
]}

Amina, Sarwat ^{[1
,2
]}

Malavasi, Fabio ^{[31
,32
]}

Huang, Eric J. ^{[33
,34
]}

Zhang, Jiasheng ^{[33
,34
]}

机构：

[1] Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, Kanazawa, Ishikawa 9208640, Japan

[2] Kanazawa Univ, 21st Century Ctr Excellence COE, Program Innovat Brain Sci Dev Learning & Memory, Kanazawa, Ishikawa 9208640, Japan

[3] Kanazawa Univ, Ctr Child Mental Dev, Osaka Hamamatsu Kanazawa Univ Joint Res Ctr, Kanazawa, Ishikawa 9208640, Japan

[4] Kanazawa Univ Hosp, Dept Child Psychiat, Kanazawa, Ishikawa 9208641, Japan

[5] Kanazawa Univ Hosp, Dept Clin Lab, Kanazawa, Ishikawa 9208641, Japan

[6] Kanazawa Univ, Grad Sch Med, Dept Psychiat & Neurobiol, Kanazawa, Ishikawa 9208640, Japan

[7] Kanazawa Univ, Grad Sch Med, Dept Internal Med, Kanazawa, Ishikawa 9208640, Japan

[8] Kanazawa Univ, Grad Sch Med, Dept Neurosurg, Kanazawa, Ishikawa 9208640, Japan

[9] Kanazawa Univ, Grad Sch Med, Dept Mol & Cellular Pathol, Kanazawa, Ishikawa 9208640, Japan

[10] Core Res Evolut Sci & Technol, Tokyo 1020075, Japan

[11] Osaka Kanazawa Hamamatsu Univ, United Grad Sch Child Dev, Osaka 5650871, Japan

[12] Hamamatsu Univ Sch Med, Dept Psychiat & Neurol, Hamamatsu, Shizuoka 4313192, Japan

[13] RIKEN Brain Sci Inst, Lab Mol Psychiat, Saitama 3510198, Japan

[14] Nanao Natl Hosp, Nanao 9208531, Japan

[15] Chonbuk Natl Univ, Sch Med, Dept Biochem, Jeonju, South Korea

[16] Chonbuk Natl Univ, Sch Med, Dept Pediat, Jeonju, South Korea

[17] Korea Adv Inst Sci & Technol, Seoul, South Korea

[18] Hokuriku Innovat Cluster Hlth Sci, Kanazawa, Ishikawa 9208640, Japan

[19] Gunma Univ, Grad Sch Med, Dept Neurophysiol, Gunma 3718511, Japan

[20] Krasnoyarsk State Med Univ, Dept Med Chem & Biochem, Krasnoyarsk 660022, Russia

[21] Krasnoyarsk State Med Univ, Dept Psychiat, Krasnoyarsk 660022, Russia

[22] Hamamatsu Univ, Ctr Child Mental Dev, Osaka Hamamatsu Kanazawa Univ Joint Res Ctr, Hamamatsu, Shizuoka 4313197, Japan

[23] Chukyo Univ, Fac Sociol, Aichi 4700393, Japan

[24] Aichi Childrens Hlth & Med Ctr, Aichi 4748710, Japan

[25] Univ Tokyo, Div Counseling & Support, Off Mental Hlth Support, Tokyo 1130033, Japan

[26] Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo 1138655, Japan

[27] Showa Univ, Sch Med, Dept Psychiat, Tokyo 1578577, Japan

[28] Osaka Univ, Mol Res Ctr, Osaka Hamamatsu Kanazawa Univ Joint Res Ctr, Osaka 5650871, Japan

[29] Kyushu Univ, Grad Sch Pharmaceut Sci, Lab Pathophysiol, Fukuoka 8128582, Japan

[30] Kyushu Univ, Grad Sch Dent Sci, Dept Oral Anat & Cell Biol, Fukuoka 8128582, Japan

[31] Univ Turin, Sch Med, Immunogenet Lab, Dept Genet Biol & Biochem, I-10126 Turin, Italy

[32] Univ Turin, Sch Med, CeRMS, I-10126 Turin, Italy

[33] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94121 USA

[34] Vet Affair Med Ctr, Pathol Serv, San Francisco, CA 94121 USA

[35] Kanazawa Univ, Inst Nat & Environm Technol, Kanazawa, Ishikawa 9201192, Japan

来源：

NEUROSCIENCE RESEARCH | 2010年 / 67卷 / 02期

基金：

日本学术振兴会;

关键词：

CD38; Oxytocin; Mutation; Polymorphism; Autism; High-functioning autism; CYCLIC ADP-RIBOSE; HIGH-FUNCTIONING AUTISM; DIAGNOSTIC INTERVIEW; SOCIAL-BEHAVIOR; BIPOLAR DISORDER; OXYTOCIN; ASSOCIATION; PREVALENCE; POPULATION; HUMANS;

D O I：

10.1016/j.neures.2010.03.004

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

引用

页码：181 / 191

页数：11

共 57 条

[1] Gene and expression analyses reveal enhanced expression of pericentrin 2 (PCNT2) in bipolar disorder [J].