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Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene

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Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene. / Munir, Sabrina; Freidin, Maxim B; Brain, Susan; Williams, Frances M K.

In: PLoS ONE, Vol. 13, No. 4, 26.04.2018, p. e0196279.

Research output: Contribution to journalArticle

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Munir, S, Freidin, MB, Brain, S & Williams, FMK 2018, 'Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene', PLoS ONE, vol. 13, no. 4, pp. e0196279. https://doi.org/10.1371/journal.pone.0196279

APA

Munir, S., Freidin, M. B., Brain, S., & Williams, F. M. K. (2018). Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene. PLoS ONE, 13(4), e0196279. https://doi.org/10.1371/journal.pone.0196279

Vancouver

Munir S, Freidin MB, Brain S, Williams FMK. Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene. PLoS ONE. 2018 Apr 26;13(4):e0196279. https://doi.org/10.1371/journal.pone.0196279

Author

Munir, Sabrina ; Freidin, Maxim B ; Brain, Susan ; Williams, Frances M K. / Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene. In: PLoS ONE. 2018 ; Vol. 13, No. 4. pp. e0196279.

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@article{9c5c0f445f4b487ca82bfccec99939d2,
title = "Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene",
abstract = "BACKGROUND: Raynaud's phenomenon (RP) describes the phenomenon of recurrent vasospasm of digital arteries, associated with skin colour changes: pallor, cyanosis and erythema. Twin studies have indicated a genetic predisposition for RP; however, the precise aetiology of RP remains unknown. It is thought that genetic variation in temperature-responsive or vasospastic genes might underlie RP so performed a candidate gene study in a large, population based sample. We assessed the association between RP and single nucleotide polymorphisms (SNPs) in the TRPA1, TRPM8, CALCA, CALCB and NOS1 genes.METHODS: Analysis included a total of 4276 individuals from the TwinsUK database. RP status had been determined using validated, self-administered questionnaires and was diagnosed in 640 individuals (17.6{\%}). 66 tag SNPs across the candidate genes were tested for association with RP status using a linear regression model, accounting for covariates. Adjustment was made for multiple testing. RegulomeDB and GTEx databases were used to assess possible functional effects of the polymorphisms.RESULTS: Nominally significant associations between RP and four SNPs in NOS1 and one in CALCB were identified. After permutation testing, rs527590 SNP in NOS1 passed the significance threshold. RegulomeDB scores indicated an unlikely functional effect of this variant, while the survey of the GTEx database found the SNP and several variants in linkage disequilibrium to be cis-eQTLs in skin.CONCLUSION: Results indicate that RP is associated with variation in gene NOS1. This finding may be related to the observation that the significant SNP in NOS1 is known to exhibit functional influence on the gene expression.",
keywords = "Raynaud’s phenomenon",
author = "Sabrina Munir and Freidin, {Maxim B} and Susan Brain and Williams, {Frances M K}",
year = "2018",
month = "4",
day = "26",
doi = "10.1371/journal.pone.0196279",
language = "English",
volume = "13",
pages = "e0196279",
journal = "PL o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene

AU - Munir, Sabrina

AU - Freidin, Maxim B

AU - Brain, Susan

AU - Williams, Frances M K

PY - 2018/4/26

Y1 - 2018/4/26

N2 - BACKGROUND: Raynaud's phenomenon (RP) describes the phenomenon of recurrent vasospasm of digital arteries, associated with skin colour changes: pallor, cyanosis and erythema. Twin studies have indicated a genetic predisposition for RP; however, the precise aetiology of RP remains unknown. It is thought that genetic variation in temperature-responsive or vasospastic genes might underlie RP so performed a candidate gene study in a large, population based sample. We assessed the association between RP and single nucleotide polymorphisms (SNPs) in the TRPA1, TRPM8, CALCA, CALCB and NOS1 genes.METHODS: Analysis included a total of 4276 individuals from the TwinsUK database. RP status had been determined using validated, self-administered questionnaires and was diagnosed in 640 individuals (17.6%). 66 tag SNPs across the candidate genes were tested for association with RP status using a linear regression model, accounting for covariates. Adjustment was made for multiple testing. RegulomeDB and GTEx databases were used to assess possible functional effects of the polymorphisms.RESULTS: Nominally significant associations between RP and four SNPs in NOS1 and one in CALCB were identified. After permutation testing, rs527590 SNP in NOS1 passed the significance threshold. RegulomeDB scores indicated an unlikely functional effect of this variant, while the survey of the GTEx database found the SNP and several variants in linkage disequilibrium to be cis-eQTLs in skin.CONCLUSION: Results indicate that RP is associated with variation in gene NOS1. This finding may be related to the observation that the significant SNP in NOS1 is known to exhibit functional influence on the gene expression.

AB - BACKGROUND: Raynaud's phenomenon (RP) describes the phenomenon of recurrent vasospasm of digital arteries, associated with skin colour changes: pallor, cyanosis and erythema. Twin studies have indicated a genetic predisposition for RP; however, the precise aetiology of RP remains unknown. It is thought that genetic variation in temperature-responsive or vasospastic genes might underlie RP so performed a candidate gene study in a large, population based sample. We assessed the association between RP and single nucleotide polymorphisms (SNPs) in the TRPA1, TRPM8, CALCA, CALCB and NOS1 genes.METHODS: Analysis included a total of 4276 individuals from the TwinsUK database. RP status had been determined using validated, self-administered questionnaires and was diagnosed in 640 individuals (17.6%). 66 tag SNPs across the candidate genes were tested for association with RP status using a linear regression model, accounting for covariates. Adjustment was made for multiple testing. RegulomeDB and GTEx databases were used to assess possible functional effects of the polymorphisms.RESULTS: Nominally significant associations between RP and four SNPs in NOS1 and one in CALCB were identified. After permutation testing, rs527590 SNP in NOS1 passed the significance threshold. RegulomeDB scores indicated an unlikely functional effect of this variant, while the survey of the GTEx database found the SNP and several variants in linkage disequilibrium to be cis-eQTLs in skin.CONCLUSION: Results indicate that RP is associated with variation in gene NOS1. This finding may be related to the observation that the significant SNP in NOS1 is known to exhibit functional influence on the gene expression.

KW - Raynaud’s phenomenon

U2 - 10.1371/journal.pone.0196279

DO - 10.1371/journal.pone.0196279

M3 - Article

C2 - 29698501

VL - 13

SP - e0196279

JO - PL o S One

JF - PL o S One

SN - 1932-6203

IS - 4

ER -

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