The neuropeptide genes TAC1, TAC3, TAC4, VIP and PACAP(ADCYAP1), and susceptibility to multiple sclerosis

Cunningham, Stephen; O’Doherty, Catherine; Patterson, Chris; McDonnell, Gavin; Hawkins, Stanley; Marrosu, Maria Giovanna; Vandenbroeck, Koen

doi:10.1016/j.jneuroim.2006.11.002

Cited by 13 publications

(12 citation statements)

References 30 publications

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“…Even though sP is functionally linked to TRPV1, Tac1 SNPs showed no bias in our patient population. In retrospect, our failure to find relevant Tac1 SNPs should not surprise, given our comparison within a disease population rather than comparing patients with normal controls as before (46,47), and it coincides with the lack of EAE protection observed here in Tac1 -/-mice.…”

Section: Discussionsupporting

confidence: 70%

TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis

Paltser

Liu

Yantha

et al. 2013

Mol Med

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Multiple sclerosis (MS) is a chronic progressive, demyelinating condition whose therapeutic needs are unmet, and whose pathoetiology is elusive. We report that transient receptor potential vanilloid-1 (TRPV1) expressed in a major sensory neuron subset, controls severity and progression of experimental autoimmune encephalomyelitis (EAE) in mice and likely in primary progressive MS. TRPV1 -/-B6 congenics are protected from EAE. Increased survival reflects reduced central nervous systems (CNS) infiltration, despite indistinguishable T cell autoreactivity and pathogenicity in the periphery of TRPV1-sufficient and -deficient mice. The TRPV1 + neurovascular complex defining the blood-CNS barriers promoted invasion of pathogenic lymphocytes without the contribution of TRPV1-dependent neuropeptides such as substance P . In MS patients, we found a selective risk-association of the missense rs877610 TRPV1 single nucleotide polymorphism (SNP) in primary progressive disease. Our findings indicate that TRPV1 is a critical disease modifier in EAE, and we identify a predictor of severe disease course and a novel target for MS therapy.

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Section: Discussionsupporting

confidence: 70%

TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis

Paltser

Liu

Yantha

et al. 2013

Mol Med

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“…In our study, being homozygous for the rare G allele of TAC1 rs2072100 was associated with a 2.11-fold higher odds of belonging to the Lower Energy class. While the rs2072100 polymorphism was linked with increased risk for colorectal cancer 103 and susceptibility to multiple sclerosis, 104 no studies were identified that reported on associations with energy.…”

Section: Discussionmentioning

confidence: 99%

Associations Between Neurotransmitter Genes and Fatigue and Energy Levels in Women After Breast Cancer Surgery

Eshragh

Dhruva

Paul

et al. 2017

Journal of Pain and Symptom Management

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Context Fatigue is a common problem in oncology patients. Less is known about decrements in energy levels and the mechanisms that underlie both fatigue and energy. Objectives In patients with breast cancer, variations in neurotransmitter genes between Lower and Higher Fatigue latent classes and between the Higher and Lower Energy latent classes were evaluated. Methods Patients completed assessments prior to and monthly for 6 months following surgery. Growth mixture modeling was used to identify distinct latent classes for fatigue severity and energy levels. Thirty candidate genes involved in various aspects of neurotransmission were evaluated. Results Eleven single nucleotide polymorphisms (SNPs) or haplotypes (i.e., ADRB2 rs1042718, BDNF rs6265, COMT rs9332377, CYP3A4 rs4646437, GALR1 rs949060, GCH1 rs3783642, NOS1 rs9658498, NOS1 rs2293052, NPY1R Haplotype A04, SLC6A2 rs17841327 and 5HTTLPR + rs25531 in SLC6A4) were associated with latent class membership for fatigue. Seven SNPs or haplotypes (i.e., NOS1 rs471871, SLC6A1 rs2675163, SLC6A1 Haplotype D01, SLC6A2 rs36027, SLC6A3 rs37022, SLC6A4 rs2020942, and TAC1 rs2072100) were associated with latent class membership for energy. Three of thirteen genes (i.e., NOS1, SLC6A2, SLC6A4) were associated with latent class membership for both fatigue and energy. Conclusions Molecular findings support the hypothesis that fatigue and energy are distinct, yet related symptoms. Results suggest that a large number of neurotransmitters play a role in the development and maintenance of fatigue and energy levels in breast cancer patients.

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“…This is the first report to describe a genetic association of VIP or of its 2 VIP receptors with any autoimmune disorder. Reduced levels of VIP and altered expression of VPAC 2 in T cells from patients with multiple sclerosis were recently reported (9); however, results of 2 different studies have failed to support the notion of genetic polymorphisms within the VIP and VPAC 2 genes in that disease (8,9).…”

Section: Discussionmentioning

confidence: 99%

“…Although studies have been undertaken in an effort to correlate altered VIP levels, presence of VIP autoantibodies, or VIP genetic variants with severity and incidence of autoimmunity, no association has been conclusively demonstrated (6)(7)(8)(9). We hypothesized that the exacerbated inflammatory autoimmune response in RA might result directly from altered expression and/or signaling of VIP receptors in immune cells.…”

mentioning

confidence: 99%