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

Toshio Munesue, Shigeru Yokoyama, Kazuhiko Nakamura, Ayyappan Anitha, Kazuo Yamada, Kenshi Hayashi, Tomoya Asaka, Hong Xiang Liu, Duo Jin, Keita Koizumi, Mohammad Saharul Islam, Jian Jun Huang, Wen Jie Ma, Uh Hyun Kim, Sun Jun Kim, Keunwan Park, Dongsup Kim, Mitsuru Kikuchi, Yasuki Ono, Hideo NakataniShiro Suda, Taishi Miyachi, Hirokazu Hirai, Alla Salmina, Yu A. Pichugina, Andrei A. Soumarokov, Nori Takei, Norio Mori, Masatsugu Tsujii, Toshiro Sugiyama, Kunimasa Yagi, Masakazu Yamagishi, Tsukasa Sasaki, Hidenori Yamasue, Nobumasa Kato, Ryota Hashimoto, Masako Taniike, Yutaka Hayashi, Junichiro Hamada, Shioto Suzuki, Akishi Ooi, Mami Noda, Yuko Kamiyama, Mizuho A. Kido, Olga Lopatina, Minako Hashii, Sarwat Amina, Fabio Malavasi, Eric J. Huang, Jiasheng Zhang, Nobuaki Shimizu, Takeo Yoshikawa, Akihiro Matsushima, Yoshio Minabe, Haruhiro Higashida

Research output: Contribution to journalArticlepeer-review

164 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)181-191
Number of pages11
JournalNeuroscience Research
Issue number2
Publication statusPublished - Jun 2010

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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