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Association Study between the CD157/BST1 Gene and Autism Spectrum Disorders in a Japanese Population.

ABSTRACT: CD157, also referred to as bone marrow stromal cell antigen-1 (BST-1), is a glycosylphosphatidylinositol-anchored molecule that promotes pre-B-cell growth. Previous studies have reported associations between single-nucleotide polymorphisms (SNPs) of the CD157/BST1 gene with Parkinson's disease. In an attempt to determine whether SNPs or haplotypes in the CD157/BST1 are associated with other brain disorders, we performed a case-control study including 147 autism spectrum disorder (ASD) patients at Kanazawa University Hospital in Japan and 150 unselected Japanese volunteers by the sequence-specific primer-polymerase chain reaction method combined with fluorescence correlation spectroscopy. Of 93 SNPs examined, two SNPs showed significantly higher allele frequencies in cases with ASDs than in unaffected controls (rs4301112, OR = 6.4, 95% CI = 1.9 to 22, p = 0.0007; and rs28532698, OR = 6.2, 95% CI = 1.8 to 21, p = 0.0012; Fisher's exact test; p < 0.002 was considered significant after multiple testing correction). In addition, CT genotype in rs10001565 was more frequently observed in the ASD group than in the control group (OR = 15, 95% CI = 2.0 to 117, p = 0.0007; Fisher's exact test). The present data indicate that genetic variation of the CD157/BST1 gene might confer susceptibility to ASDs.

SUBMITTER: Yokoyama S

PROVIDER: S-EPMC4493464 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Association Study between the CD157/BST1 Gene and Autism Spectrum Disorders in a Japanese Population.

Yokoyama Shigeru S Al Mahmuda Naila N Munesue Toshio T Hayashi Kenshi K Yagi Kunimasa K Yamagishi Masakazu M Higashida Haruhiro H

Brain sciences 20150520 2

CD157, also referred to as bone marrow stromal cell antigen-1 (BST-1), is a glycosylphosphatidylinositol-anchored molecule that promotes pre-B-cell growth. Previous studies have reported associations between single-nucleotide polymorphisms (SNPs) of the CD157/BST1 gene with Parkinson's disease. In an attempt to determine whether SNPs or haplotypes in the CD157/BST1 are associated with other brain disorders, we performed a case-control study including 147 autism spectrum disorder (ASD) patients a ...[more]

PMID: 26010484

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Project description:Importance:Autism spectrum disorders (ASD) are characterized by impairments in social interaction, communication, and repetitive or restrictive behavior. Although multiple physiologic and biochemical studies have reported defects in mitochondrial oxidative phosphorylation in patients with ASD, the role of mitochondrial DNA (mtDNA) variation has remained relatively unexplored. Objective:To assess what impact mitochondrial lineages encompassing ancient mtDNA functional polymorphisms, termed haplogroups, have on ASD risk. Design, Setting, and Participants:In this cohort study, individuals with autism and their families were studied using the Autism Genetic Resource Exchange cohort genome-wide association studies data previously generated at the Children's Hospital of Philadelphia. From October 2010 to January 2017, we analyzed the data and used the mtDNA single-nucleotide polymorphisms interrogated by the Illumina HumanHap 550 chip to determine the mtDNA haplogroups of the individuals. Taking into account the familial structure of the Autism Genetic Resource Exchange data, we then determined whether the mtDNA haplogroups correlate with ASD risk. Main Outcomes and Measures:Odds ratios of mitochondrial haplogroup as predictors of ASD risk. Results:Of 1624 patients with autism included in this study, 1299 were boys (80%) and 325 were girls (20%). Families in the Autism Genetic Resource Exchange collection (933 families, encompassing 4041 individuals: 1624 patients with ASD and 2417 healthy parents and siblings) had been previously recruited in the United States with no restrictions on age, sex, race/ethnicity, or socioeconomic status. Relative to the most common European haplogroup HHV, European haplogroups I, J, K, O-X, T, and U were associated with increased risk of ASD, as were Asian and Native American haplogroups A and M, with odds ratios ranging from 1.55 (95% CI, 1.16-2.06) to 2.18 (95% CI, 1.59-3) (adjusted P < .04). Hence, mtDNA haplogroup variation is an important risk factor for ASD. Conclusions and Relevance:Because haplogroups I, J, K, O-X, T, and U encompass 55% of the European population, mtDNA lineages must make a significant contribution to overall ASD risk.

Project description:Parkinson's disease (PD), a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B) inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions. A single administration of selegiline (1-10 mg/kg) dose-dependently reduced immobility time in the forced swimming test (FST) in CD157 KO mice, but not C57BL/6N wild-type (WT) mice. At 10 mg/kg, but not 3 mg/kg, selegiline significantly increased climbing time in CD157 KO mice. A single administration of the antiparkinsonian drugs pramipexole (a dopamine (DA) D2/D3 receptor agonist) or rasagiline (another MAO-B inhibitor), and repeated injections of a noradrenergic and specific serotonergic antidepressant (NaSSA), mirtazapine, also decreased immobility time, but did not increase climbing time, in CD157 KO mice. The antidepressant-like effects of 10 mg/kg selegiline were comparable to those of 10 mg/kg rasagiline, and tended to be stronger than those of 1 mg/kg rasagiline. After the FST, CD157 KO mice showed decreases in striatal and hippocampal serotonin (5-HT) content, cortical norepinephrine (NE) content, and plasma corticosterone concentration. A single administration of selegiline at 10 mg/kg returned striatal 5-HT, cortical NE, and plasma corticosterone levels to those observed in WT mice. In the open field test (OFT), repeated administration of mirtazapine had anxiolytic effects, and selegiline nonsignificantly ameliorated anxiety-like behaviors in CD157 KO mice. In the social interaction and preference tests, repeated mirtazapine ameliorated the high anxiety and low sociability of CD157 KO mice, whereas selegiline did not. These results indicate that selegiline has antidepressant and mild anxiolytic effects in CD157 KO mice, and suggest that it is an effective antiparkinsonian drug for depressive and anxiety symptoms in PD patients with a CD157 single nucleotide polymorphism (SNP).

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Dataset Information

Association Study between the CD157/BST1 Gene and Autism Spectrum Disorders in a Japanese Population.

Publications

Association Study between the CD157/BST1 Gene and Autism Spectrum Disorders in a Japanese Population.

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