A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro

Yagui, Kazuo; Shimada, Fumiyuki; Mimura, M.; Hashimoto, Naotake; Suzuki, Yoshiyuki; Tokuyama, Yoshiharu; Nata, Koji; Tohgo, Akira; Ikehata, F.; Takasawa, Shin; Okamoto, Hiroshi; Makino, Hideichi; Saitō, Yasushi; Kanatsuka, Azuma

doi:10.1007/s001250051026

Cited by 71 publications

(66 citation statements)

References 29 publications

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“…7 of Munesue et al, 2010). As expected, the mutant R140W-CD38 showed one-third of the ADP-ribosyl cyclase activity of R140 CD38 when expressed in CHO cells (Yagui et al, 1998). In addition, social amnesia was not rescued by the local expression of human R140W-CD38, via a lentiviral infection, in the hypothalamus of CD38 knockout mice (Fig.…”

Section: Exonic Rs1800561 Snp (R140w)supporting

confidence: 75%

CD38 and its role in oxytocin secretion and social behavior

Higashida

Yokoyama

Kikuchi

et al. 2012

Hormones and Behavior

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Here, we review the functional roles of cyclic ADP-ribose and CD38, a transmembrane protein with ADP-ribosyl cyclase activity, in mouse social behavior via the regulation of oxytocin (OXT) release, an essential component of social cognition.Herein we describe data detailing the molecular mechanism of CD38-dependent OXT secretion in CD38 knockout mice. We also review studies that used OXT, OXT receptor (OXTR), or CD38 knockout mice. Additionally, we compare the behavioral impairments that occur in these knockout mice in relation to the OXT system and CD38.This review also examines autism spectrum disorder (ASD), which is characterized by social and communication impairments, in relation to defects in the OXT system. Two single nucleotide polymorphisms (SNPs) in the human CD38 gene are possible risk factors for ASD via inhibition of OXT function. Further analysis of CD38 in relation to the OXT system may provide a better understanding of the neuroendocrinological roles of OXT and CD38 in the hypothalamus and of the pathophysiology of ASD.3

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Section: Exonic Rs1800561 Snp (R140w)supporting

confidence: 75%

CD38 and its role in oxytocin secretion and social behavior

Higashida

Yokoyama

Kikuchi

et al. 2012

Hormones and Behavior

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“…With regard to genetic factors, another study [26] screened for mutations in the CD38 gene and reported a missense mutation causing an Arg140 to Trp aminoacid substitution in exon 3 in 4 of 31 Japanese Type II diabetic subjects who had first-degree and/or seconddegree relatives with Type II diabetes (but in none of the 90 Japanese control subjects). CD38 enzyme activity studies using COS-7 cells expressing the Arg140Trp mutation showed reductions in ADP-ribosyl cyclase and cADPR hydrolase activities of about 50%.…”

Section: Discussionmentioning

confidence: 99%

“…We typed two published polymorphisms in all Type II diabetic and control subjects (n=398). The C→T polymorphism at codon 140 of exon 3 (Arg140Trp) was typed according to another study [26]. Briefly, 12 µl of the PCR fragments were digested at 65°C for 3 h with 0.…”

Section: Detection Of Anti-cd38 Antibodiesmentioning

confidence: 99%

“…By PCR-SSCP in 44 Type II diabetic patients, no mutations were found in any of the eight exons, the 5′ end of intron 1 or the 5′ and 3′ untranslated regions of the CD38 gene. The missense mutation found by another study [26] in exon 3 was also screened for in all Type II diabetic and control subjects (n=398), and was found in none. The allele frequency of the PvUII genotype was 18.4% for the undigested allele A and 81.6% for the digested allele B.…”

Section: Detection Of Anti-cd38 Antibodies In Human Serummentioning

confidence: 99%

“…However, the genetic factors are largely unknown except for mutations causing monogenic forms of diabetes, which have been shown in the insulin, insulin receptor, glucokinase and mitochondrial genes together with genes for several transcription factors [24,25]. Recently, another study [26] that screened for mutations in the CD38 gene, reported a missense mutation causing an aminoacid substitution -Arg140Trp -in exon 3 in 4 out of 31 Type II diabetic Japanese patients but in none of the control subjects. Furthermore, a different study [27] reported a bi-allelic restriction-fragment length polymorphism (RFLP) in intron 1 for the enzyme PvUII in Italian patients.…”

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confidence: 99%

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Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

et al. 2002

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Aims/hypothesis. Autoantibodies against CD38 have been found in some patients with Type II (non-insulindependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i) overlaps with anti-GAD autoimmunity, (ii) identifies an insulin-deficient phenotype, (iii) is under the influence of genetic factors. Methods. We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects).Results. CD38-autoantibodies were found in 8.4% of Type II diabetic patients (p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD38ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti-CD38 positive had DQB1*02 compared with 38% of anti-CD38 negative (p=0.04).On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired (p=0.02) only in association with anti-GAD positivity (3.2±3.1 U/mol, mean ± SD) but not in anti-CD38 positive patients (5.6±2.9) as compared with patients free of autoimmunity (4.5±4.6, p=NS).In 44 Type II diabetic patients (22 negative and 22 positive for anti-CD38), no mutations were detected in any of the 8 exons, 5′ end of intron 1 or the 5′ and 3′ untranslated regions of the CD38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. Conclusion. Anti-CD38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence. [Diabetologia (2002[Diabetologia ( ) 45:1298[Diabetologia ( -1306

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CD 38

Okamoto

Takasawa

2002

Wiley Encyclopedia of Molecular Medicine

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A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro

Cited by 71 publications

References 29 publications

CD38 and its role in oxytocin secretion and social behavior

CD38 and its role in oxytocin secretion and social behavior

Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

CD 38

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