Analysis of variations in the NAPG gene on chromosome 18p11 in bipolar disorder

Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Psychiatric Genetics (Impact Factor: 1.94). 03/2006; 16(1):3-8. DOI: 10.1097/01.ypg.0000180678.88169.b0
Source: PubMed


A number of studies have implicated the chromosome 18p11 region as a susceptibility region for bipolar disorder. The gene encoding gamma-SNAP (NAPG), one of three soluble N-ethylmaleimide-sensitive fusion (NSF)-attachment proteins (SNAPs), is located in the 18p11 region and is thought to play a role in cellular processes required for neurotransmission in the central nervous system. The purpose of this study is to investigate whether polymorphisms in the human NAPG gene contribute to the etiology of bipolar disorder.
To test this hypothesis, we used a case-control design in which the genotype and allele frequencies for five single-nucleotide polymorphisms in the human NAPG gene were compared between individuals with a diagnosis of type I bipolar disorder (n=460) and control individuals (n=191).
The genotype results indicate that three of the single-nucleotide polymorphisms in the NAPG gene, rs2290279 (P=0.027), rs495484 (P=0.044) and rs510110 (P=0.046), show a nominal, statistically significant association with bipolar disorder at the genotype frequency level.
The results of this study suggest that polymorphisms in the human NAPG gene may represent risk factors for the development of bipolar disorder, but before such a role can be established, the results of this study must be confirmed in additional populations of bipolar disorder patients and controls.

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    • "Chromosomal locus 18p11.2 harbors many candidate genes like NAPG[28] GNAL[29] NDUFV2[24] and VAPA.[30] It may be possible that this marker is directly or indirectly involved in the regulation of neighboring genes. "
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    ABSTRACT: The aim of our study was to investigate whether the tandem repeat polymorphism in D18S452 microsatellite marker at locus 18p11.2 is a risk factor of bipolar affective disorder (BPAD) in Kashmiri population. The repeat polymorphism in D18S452 was evaluated by polymerase chain reaction (PCR) analysis of in 74 diagnosed BPAD patients and 74 controls subjects. Tandem repeat (300 bp*) allele frequency was found to be 1.35% in controls and 8.108% in cases. The tandem repeat (250 bp*) allele frequency was found to be in 91.89% in cases and 98.65% in controls. The 252 bp/252 bp genotype was found to be present in 89.18% of cases and 98.64% of controls, the 300 bp/300 bp genotype in 5.40% of cases and 1.35% of controls and the 252 bp/300 bp variant in 5.40% of cases and none among the controls. Although the proportion of patients homozygous for tandem repeat (300 bp/300 bp) was higher in cases than in controls, the difference was not statistically significant when 252 bp/252 bp genotype was taken as reference (odds ratio [OR]=4.4242; 95% confidence interval [CI] 0.4822-40.5924); P=0.1529). However, when the frequency of heterozygous genotype (252 bp/300 bp) was compared with 252 bp/252 bp statistical significance was observed (OR=8.0603; 95% CI 1.1112-58.4646; P=0.0383). This is the first study reporting a significant association between D18S452 maker with tandem repeat polymorphism in heterozygous condition (252 bp/300 bp) and the development of BPAD in Kashmiri population.
    Indian Journal of Psychiatry 10/2013; 55(4):371-5. DOI:10.4103/0019-5545.120567
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    • "Note that total number of subjects was 13, however, one subject was 17 months old, thus was left out of no. of assessed in disorders that this subject was too young to be diagnosed with. Mukherjee et al., 2006] and candidate genes (TGIF [Chavarr ıa-Siles et al., 2007], NDUFV2 [Wasizuka et al., 2009], VAPA [Lohoff et al., 2008], NAPG [Weller et al., 2006], IMPA2 [Yoshikawa et al., 2001; Sjøholt et al., 2004], GNAL [Tsiouris et al., 1996]) related to schizophrenia and bipolar disorder as being on chromosome 18p, the three 18p-subjects here showed no evidence of psychotic or affective pathology. Nevertheless, given the small sample size of 18p-subjects here, we recommend screening for psychosis and bipolar disorder, in addition to ADHD and anxiety disorders, given the above mentioned reports of linkage for these disorders to chromosome 18p and at least one previous report of psychosis in a subject with an 18p-deletion [Babovic-Vuksanovic et al., 2004]. "
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    ABSTRACT: Chromosome 18 abnormalities are associated with a range of physical abnormalities such as short stature and hearing impairments. Psychiatric manifestations have also been observed. This study focuses on the presentations of psychiatric syndromes as they relate to specific chromosomal abnormalities of chromosome 18. Twenty-five subjects (13 with an 18q deletion, 9 with 18p tetrasomy, and 3 with an 18p deletion), were interviewed by psychiatrists (blind to specific chromosomal abnormality) using the DIGS (subjects 18 and older) or KSADS-PL (subjects under 18). A consensus best estimation diagnostic process was employed to determine psychiatric syndromes. Oligonucleotide Array Comparative Genomic Hybridization (Agilent Technologies) was utilized to define specific regions of chromosome 18 that were deleted or duplicated. These data were further analyzed to determine critical regions of the chromosome as they relate to phenotypic manifestations in these subjects. 58.3% of the chromosome 18q- deletion subjects had depressive symptoms, 58.3% had anxiety symptoms, 25% had manic symptoms, and 25% had psychotic symptoms. 66.6% of the chromosome 18p- deletion subjects had anxiety symptoms, and none had depressive, manic, or psychotic symptoms. Fifty percent of the chromosome 18p tetrasomy subjects had anxiety symptoms, 12.5% had psychotic symptoms, and 12.5% had a mood disorder. All three chromosomal disorders were associated with high anxiety rates. Psychotic, manic and depressive disorders were seen mostly in 18q- subjects and this may be helpful in narrowing regions for candidate genes for these psychiatric conditions.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2009; 153B(3):837-45. DOI:10.1002/ajmg.b.31047 · 3.42 Impact Factor
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    ABSTRACT: The gene of an esterase enzyme, called paraoxonase (PON, EC. is a member of a multigene family that comprises three related genes PON1, PON2, and PON3 with structural homology clustering on the chromosome 7.(1,2) The PON1 activity and the polymorphism of the PON1 and PON2 genes have been found to be associated with risk of cardiovascular diseases such as hypercholesterolaemia, non-insulin-dependent diabetes, coronary heart disease (CHD) and myocardial infaction.(3-8) The importance of cardiovascular risk factors in the pathomechanism of Alzheimer's disease (AD) and vascular dementia (VD)(9-13) prompted us to examine the genetic effect of PON2 gene codon 311 (Cys-->Ser; PON2*S) polymorphism and the relationship between the PON2*S allele and the other dementia risk factor, the apoE polymorphism in these dementias. The PON2*C and PON2*S allele frequencies were similar in both AD (25% and 75%) and VD groups (23% and 77%), respectively, compared with the controls (27% and 73%). The ratio of the PON2*S carriers was significantly higher among the apoE4 allele carrier AD (27%) and VD (25%) groups than in the control (12%). Our results indicate that the PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD.
    Molecular Psychiatry 01/2002; 7(1):110-2. DOI:10.1038/sj/mp/4000916 · 14.50 Impact Factor
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