| 11097613 | DPP6 as a candidate gene for neuroleptic-induced tardive dyskinesia. | Tanaka S, etal., Pharmacogenomics J. 2013 Feb;13(1):27-34. doi: 10.1038/tpj.2011.36. Epub 2011 Aug 9. | We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. First, we screened associations by using a genome-wide (Illumina HumanHapCNV370) SNP array in 61 Japanese schizophrenia patients with treatment-re sistant TD and 61 Japanese schizophrenia patients without TD. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. An association of an SNP in the DPP6 (dipeptidyl peptidase-like protein-6) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample (allelic P=0.008 in the replication sample, allelic P=4.6 x 10(-6), odds ratio 2.32 in the combined sample). The SNP is located in intron-1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD. | 21826085 | 2013-06-01 |
| 5687182 | Dpp6 is associated with susceptibility to progressive spinal muscular atrophy. | van Es MA, etal., Neurology. 2009 Mar 31;72(13):1184-5. | | 19332697 | 2009-02-01 |
| 11087162 | Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. | van Es MA, etal., Nat Genet. 2008 Jan;40(1):29-31. Epub 2007 Dec 16. | We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 x 10(-8) in 1,767 cases and 1,916 healthy cont rols and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18-1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies. | 18084291 | 2008-06-01 |
| 5687181 | Association between DPP6 polymorphism and the risk of sporadic amyotrophic lateral sclerosis in Chinese patients. | Li XG, etal., Chin Med J (Engl). 2009 Dec 20;122(24):2989-92. | BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease characterized by the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, which results in muscle weakness, atrophy. Sporadic ALS (SALS) accounts for about 90% of ALS cases, but the etiology is largely unknown. Most of the researchers consider it to be a complex disease. There have been several genome-wide association (GWA) studies reporting several single nucleotide polymorphisms (SNPs) which are susceptible to ALS, but no data of Asians (including Chinese) yet. We investigate whether the polymorphism of rs10260404 in DPP6 gene is associated with SALS in Chinese Han origin to compare the ethnic differences between Chinese Han origin and other populations. METHODS: The genomic DNA was extracted from the leukocytes of whole blood samples in 58 Chinese Han patients with SALS and 52 healthy controls. The asymmetric PCR was processed in the presence of an unlabeled probe that contained the rs10260404 locus. The product was genotyped on a light scanner using high resolution melting method and some were confirmed with sequencing. RESULTS: The rs10260404 polymorphism was in Hardy-Weinberg equilibrium in patients and controls. The CC genotype and the C allele were similar in patients compared with healthy subjects and not associated with an increased risk of Chinese SALS patients (chi(2) = 0.29, OR = 1.26, 95% CI 0.55 - 2.87, P > 0.05). CONCLUSIONS: The rs10260404 is not associated with ALS susceptibility in Chinese people with Han origin which may be due to ethnic differences. More study with large number of cases in Chinese population is really necessary. | 20137488 | 2009-02-01 |
| 5687188 | DPP6 gene variability confers increased risk of developing sporadic amyotrophic lateral sclerosis in Italian patients. | Del Bo R, etal., J Neurol Neurosurg Psychiatry. 2008 Sep;79(9):1085. | | 18708572 | 2008-02-01 |
| 5687186 | Haplotype-sharing analysis implicates chromosome 7q36 harboring DPP6 in familial idiopathic ventricular fibrillation. | Alders M, etal., Am J Hum Genet. 2009 Apr;84(4):468-76. Epub 2009 Mar 12. | Idiopathic Ventricular Fibrillation (IVF) is defined as spontaneous VF without any known structural or electrical heart disease. A family history is present in up to 20% of probands with the disorder, suggesting that at least a subset of IVF is hereditary. A genome-wide haplotype-sharing analysis wa s performed for identification of the responsible gene in three distantly related families in which multiple individuals died suddenly or were successfully resuscitated at young age. We identified a haplotype, on chromosome 7q36, that was conserved in these three families and was also shared by 7 of 42 independent IVF patients. The shared chromosomal segment harbors part of the DPP6 gene, which encodes a putative component of the transient outward current in the heart. We demonstrated a 20-fold increase in DPP6 mRNA levels in the myocardium of carriers as compared to controls. Clinical evaluation of 84 risk-haplotype carriers and 71 noncarriers revealed no ECG or structural parameters indicative of cardiac disease. Penetrance of IVF was high; 50% of risk-haplotype carriers experienced (aborted) sudden cardiac death before the age of 58 years. We propose DPP6 as a gene for IVF and increased DPP6 expression as the likely pathogenetic mechanism. | 19285295 | 2009-02-01 |
| 598119046 | Loss-of-function variation in the DPP6 gene is associated with autosomal dominant microcephaly and mental retardation. | Liao C, etal., Eur J Med Genet. 2013 Sep;56(9):484-9. doi: 10.1016/j.ejmg.2013.06.008. Epub 2013 Jul 5. | The molecular basis of autosomal dominant microcephaly, a disorder associated with small head circumferences that results in variable mental retardation, is largely unknown. In the present study, we conducted a variation analysis of the DPP6 gene in patients wit h autosomal dominant microcephaly and variable mental retardation. The copy number variation analysis of DPP6 was performed on DNA samples from 22 patients with microcephaly using high-resolution, array-based genomic hybridization, and sequence analysis was performed to screen mutations in another 50 microcephalic patients. Two de novo deletions and one missense mutation in familial microcephalic patients were identified. The transfection of plasmids encoding green fluorescent protein-pLLU2G-shDPP6 fusion proteins in mouse brains revealed that the decreased expression of the DPP6 gene slightly reduced the weight of the mouse brains and resulted in mouse learning disabilities compared with their wild-type littermates. Our data indicate that the loss-of-function variations in DPP6 are associated with autosomal dominant microcephaly and mental retardation. DPP6 appears to play a major role in the regulation of proliferation and migration of neurons in neurogenesis, most likely by participating in neuronal electrical excitability, synaptic integration, and plasticity. | 23832105 | 2013-09-01 |
