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Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients

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Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients. / Natarajan, Renuka; Einarsdottir, Elisabet; Riutta, Asko; Hagman, Sanna; Raunio, Minna; Mononen, Nina; Lehtimäki, Terho; Elovaara, Irina.

In: JOURNAL OF NEUROIMMUNOLOGY, Vol. 250, No. 1-2, 15.09.2012, p. 106-110.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Natarajan, R, Einarsdottir, E, Riutta, A, Hagman, S, Raunio, M, Mononen, N, Lehtimäki, T & Elovaara, I 2012, 'Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients', JOURNAL OF NEUROIMMUNOLOGY, vol. 250, no. 1-2, pp. 106-110. https://doi.org/10.1016/j.jneuroim.2012.05.014

APA

Natarajan, R., Einarsdottir, E., Riutta, A., Hagman, S., Raunio, M., Mononen, N., ... Elovaara, I. (2012). Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients. JOURNAL OF NEUROIMMUNOLOGY, 250(1-2), 106-110. https://doi.org/10.1016/j.jneuroim.2012.05.014

Vancouver

Natarajan R, Einarsdottir E, Riutta A, Hagman S, Raunio M, Mononen N et al. Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients. JOURNAL OF NEUROIMMUNOLOGY. 2012 Sep 15;250(1-2):106-110. https://doi.org/10.1016/j.jneuroim.2012.05.014

Author

Natarajan, Renuka ; Einarsdottir, Elisabet ; Riutta, Asko ; Hagman, Sanna ; Raunio, Minna ; Mononen, Nina ; Lehtimäki, Terho ; Elovaara, Irina. / Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients. In: JOURNAL OF NEUROIMMUNOLOGY. 2012 ; Vol. 250, No. 1-2. pp. 106-110.

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@article{bdd8a075bb0d4c2bbc3d3faa9967c06c,
title = "Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients",
abstract = "In this study we investigated the relationship between melatonin pathway and multiple sclerosis (MS) in a high-risk Finnish population by studying the single nucleotide polymorphisms (SNPs) in the genes coding for critical enzymes and receptors involved in the melatonin pathway. A total of 590 subjects (193 MS patients and 397 healthy controls) were genotyped for seven SNPs in four genes including tryptophan hydroxylases (TPH)1 and 2, arylalkylamine N-acetyltransferase (AANAT) and melatonin receptor 1B (MTNR1B). An overrepresentation of T allele carriers of a functional polymorphism (G-703T, rs4570625) in the promoter region of TPH2 gene was observed in the progressive MS subtypes. The haplotype rs4570625-rs10506645TT of TPH2 gene was associated with the risk of severe disability in primary progressive MS (PPMS), while haplotype rs4570625-rs10506645TC appeared to be protective against disability in secondary progressive MS (SPMS). In the MTNR1B gene, the haplotype rs10830963-rs4753426GC was associated with the risk of SPMS, whereas another haplotype rs10830963-rs4753426GT showed an association with the risk of PPMS. These data showing the association of polymorphisms in the TPH2 and MTNR1B genes with the progressive subtypes of MS and disability suggest dysregulation in melatonin pathway. Melatonin pathway seems to be involved in disease progression, and therefore its potential effects in overcoming MS-related neurodegeneration may be worth evaluating in future clinical trials.",
keywords = "Expanded Disability Status Scale (EDSS), Melatonin pathway genes, MTNR1B, Multiple sclerosis, Single nucleotide polymorphisms (SNPs), TPH2",
author = "Renuka Natarajan and Elisabet Einarsdottir and Asko Riutta and Sanna Hagman and Minna Raunio and Nina Mononen and Terho Lehtim{\"a}ki and Irina Elovaara",
year = "2012",
month = "9",
day = "15",
doi = "10.1016/j.jneuroim.2012.05.014",
language = "English",
volume = "250",
pages = "106--110",
journal = "JOURNAL OF NEUROIMMUNOLOGY",
issn = "0165-5728",
publisher = "Elsevier",
number = "1-2",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Melatonin pathway genes are associated with progressive subtypes and disability status in multiple sclerosis among Finnish patients

AU - Natarajan, Renuka

AU - Einarsdottir, Elisabet

AU - Riutta, Asko

AU - Hagman, Sanna

AU - Raunio, Minna

AU - Mononen, Nina

AU - Lehtimäki, Terho

AU - Elovaara, Irina

PY - 2012/9/15

Y1 - 2012/9/15

N2 - In this study we investigated the relationship between melatonin pathway and multiple sclerosis (MS) in a high-risk Finnish population by studying the single nucleotide polymorphisms (SNPs) in the genes coding for critical enzymes and receptors involved in the melatonin pathway. A total of 590 subjects (193 MS patients and 397 healthy controls) were genotyped for seven SNPs in four genes including tryptophan hydroxylases (TPH)1 and 2, arylalkylamine N-acetyltransferase (AANAT) and melatonin receptor 1B (MTNR1B). An overrepresentation of T allele carriers of a functional polymorphism (G-703T, rs4570625) in the promoter region of TPH2 gene was observed in the progressive MS subtypes. The haplotype rs4570625-rs10506645TT of TPH2 gene was associated with the risk of severe disability in primary progressive MS (PPMS), while haplotype rs4570625-rs10506645TC appeared to be protective against disability in secondary progressive MS (SPMS). In the MTNR1B gene, the haplotype rs10830963-rs4753426GC was associated with the risk of SPMS, whereas another haplotype rs10830963-rs4753426GT showed an association with the risk of PPMS. These data showing the association of polymorphisms in the TPH2 and MTNR1B genes with the progressive subtypes of MS and disability suggest dysregulation in melatonin pathway. Melatonin pathway seems to be involved in disease progression, and therefore its potential effects in overcoming MS-related neurodegeneration may be worth evaluating in future clinical trials.

AB - In this study we investigated the relationship between melatonin pathway and multiple sclerosis (MS) in a high-risk Finnish population by studying the single nucleotide polymorphisms (SNPs) in the genes coding for critical enzymes and receptors involved in the melatonin pathway. A total of 590 subjects (193 MS patients and 397 healthy controls) were genotyped for seven SNPs in four genes including tryptophan hydroxylases (TPH)1 and 2, arylalkylamine N-acetyltransferase (AANAT) and melatonin receptor 1B (MTNR1B). An overrepresentation of T allele carriers of a functional polymorphism (G-703T, rs4570625) in the promoter region of TPH2 gene was observed in the progressive MS subtypes. The haplotype rs4570625-rs10506645TT of TPH2 gene was associated with the risk of severe disability in primary progressive MS (PPMS), while haplotype rs4570625-rs10506645TC appeared to be protective against disability in secondary progressive MS (SPMS). In the MTNR1B gene, the haplotype rs10830963-rs4753426GC was associated with the risk of SPMS, whereas another haplotype rs10830963-rs4753426GT showed an association with the risk of PPMS. These data showing the association of polymorphisms in the TPH2 and MTNR1B genes with the progressive subtypes of MS and disability suggest dysregulation in melatonin pathway. Melatonin pathway seems to be involved in disease progression, and therefore its potential effects in overcoming MS-related neurodegeneration may be worth evaluating in future clinical trials.

KW - Expanded Disability Status Scale (EDSS)

KW - Melatonin pathway genes

KW - MTNR1B

KW - Multiple sclerosis

KW - Single nucleotide polymorphisms (SNPs)

KW - TPH2

UR - http://www.scopus.com/inward/record.url?scp=84864838067&partnerID=8YFLogxK

U2 - 10.1016/j.jneuroim.2012.05.014

DO - 10.1016/j.jneuroim.2012.05.014

M3 - Article

VL - 250

SP - 106

EP - 110

JO - JOURNAL OF NEUROIMMUNOLOGY

JF - JOURNAL OF NEUROIMMUNOLOGY

SN - 0165-5728

IS - 1-2

ER -