KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

Lara Bossini-Castillo; Carmen P Simeon; Lorenzo Beretta; Jasper Broen; Madelon C Vonk; José Luis Callejas; Patricia Carreira; Luis Rodríguez-Rodríguez; Rosa García-Portales; Miguel A González-Gay; Ivan Castellví; María Teresa Camps; Carlos Tolosa; Esther Vicente-Rabaneda; María Victoria Egurbide; Annemie J Schuerwegh; Roger Hesselstrand; Claudio Lunardi; Jacob M van Laar; Paul Shiels; Ariane Herrick; Jane Worthington; Christopher Denton; Timothy R D J Radstake; Carmen Fonseca; Javier Martin

doi:10.1186/ar4124

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

Lara Bossini-Castillo, Carmen P Simeon, Lorenzo Beretta, Jasper Broen, Madelon C Vonk, José Luis Callejas, Patricia Carreira, Luis Rodríguez-Rodríguez, Rosa García-Portales, Miguel A González-Gay, Ivan Castellví, María Teresa Camps, Carlos Tolosa, Esther Vicente-Rabaneda, María Victoria Egurbide, Annemie J Schuerwegh, Roger Hesselstrand, Claudio Lunardi, Jacob M van Laar, Paul ShielsAriane Herrick, Jane Worthington, Christopher Denton, Timothy R D J Radstake, Carmen Fonseca, Javier Martin,

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

INTRODUCTION: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort.

METHODS: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay.

RESULTS: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients.

CONCLUSIONS: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.

Original language	English
Pages (from-to)	R273
Number of pages	1
Journal	Arthritis research & therapy
Volume	14
Issue number	6
DOIs	https://doi.org/10.1186/ar4124
Publication status	Published - 27 Dec 2012

Keywords

Cohort Studies
European Continental Ancestry Group
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Hypertension, Pulmonary
Italy
Kv1.5 Potassium Channel
Linkage Disequilibrium
Netherlands
Odds Ratio
Polymorphism, Single Nucleotide
Scleroderma, Systemic
Spain
Sweden
United Kingdom
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

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10.1186/ar4124

http://www.ncbi.nlm.nih.gov/pubmed/23270786

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Bossini-Castillo, L., Simeon, C. P., Beretta, L., Broen, J., Vonk, M. C., Callejas, J. L., Carreira, P., Rodríguez-Rodríguez, L., García-Portales, R., González-Gay, M. A., Castellví, I., Camps, M. T., Tolosa, C., Vicente-Rabaneda, E., Egurbide, M. V., Schuerwegh, A. J., Hesselstrand, R., Lunardi, C., van Laar, J. M. (2012). KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor. Arthritis research & therapy, 14(6), R273. https://doi.org/10.1186/ar4124

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title = "KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor",

abstract = "INTRODUCTION: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort.METHODS: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay.RESULTS: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients.CONCLUSIONS: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.",

keywords = "Cohort Studies, European Continental Ancestry Group, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Hypertension, Pulmonary, Italy, Kv1.5 Potassium Channel, Linkage Disequilibrium, Netherlands, Odds Ratio, Polymorphism, Single Nucleotide, Scleroderma, Systemic, Spain, Sweden, United Kingdom, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't",

author = "Lara Bossini-Castillo and Simeon, {Carmen P} and Lorenzo Beretta and Jasper Broen and Vonk, {Madelon C} and Callejas, {Jos{\'e} Luis} and Patricia Carreira and Luis Rodr{\'i}guez-Rodr{\'i}guez and Rosa Garc{\'i}a-Portales and Gonz{\'a}lez-Gay, {Miguel A} and Ivan Castellv{\'i} and Camps, {Mar{\'i}a Teresa} and Carlos Tolosa and Esther Vicente-Rabaneda and Egurbide, {Mar{\'i}a Victoria} and Schuerwegh, {Annemie J} and Roger Hesselstrand and Claudio Lunardi and {van Laar}, {Jacob M} and Paul Shiels and Ariane Herrick and Jane Worthington and Christopher Denton and Radstake, {Timothy R D J} and Carmen Fonseca and Javier Martin",

year = "2012",

month = dec,

day = "27",

doi = "10.1186/ar4124",

language = "English",

volume = "14",

pages = "R273",

journal = "Arthritis research & therapy",

issn = "1478-6354",

publisher = "BioMed Central Ltd.",

number = "6",

}

Bossini-Castillo, L, Simeon, CP, Beretta, L, Broen, J, Vonk, MC, Callejas, JL, Carreira, P, Rodríguez-Rodríguez, L, García-Portales, R, González-Gay, MA, Castellví, I, Camps, MT, Tolosa, C, Vicente-Rabaneda, E, Egurbide, MV, Schuerwegh, AJ, Hesselstrand, R, Lunardi, C, van Laar, JM, Shiels, P, Herrick, A, Worthington, J, Denton, C, Radstake, TRDJ, Fonseca, C, Martin, J 2012, 'KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor', Arthritis research & therapy, vol. 14, no. 6, pp. R273. https://doi.org/10.1186/ar4124

TY - JOUR

T1 - KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

AU - Bossini-Castillo, Lara

AU - Simeon, Carmen P

AU - Beretta, Lorenzo

AU - Broen, Jasper

AU - Vonk, Madelon C

AU - Callejas, José Luis

AU - Carreira, Patricia

AU - Rodríguez-Rodríguez, Luis

AU - García-Portales, Rosa

AU - González-Gay, Miguel A

AU - Castellví, Ivan

AU - Camps, María Teresa

AU - Tolosa, Carlos

AU - Vicente-Rabaneda, Esther

AU - Egurbide, María Victoria

AU - Schuerwegh, Annemie J

AU - Hesselstrand, Roger

AU - Lunardi, Claudio

AU - van Laar, Jacob M

AU - Shiels, Paul

AU - Herrick, Ariane

AU - Worthington, Jane

AU - Denton, Christopher

AU - Radstake, Timothy R D J

AU - Fonseca, Carmen

AU - Martin, Javier

PY - 2012/12/27

Y1 - 2012/12/27

N2 - INTRODUCTION: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort.METHODS: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay.RESULTS: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients.CONCLUSIONS: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.

AB - INTRODUCTION: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort.METHODS: The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay.RESULTS: Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients.CONCLUSIONS: Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.

KW - Cohort Studies

KW - European Continental Ancestry Group

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Hypertension, Pulmonary

KW - Italy

KW - Kv1.5 Potassium Channel

KW - Linkage Disequilibrium

KW - Netherlands

KW - Odds Ratio

KW - Polymorphism, Single Nucleotide

KW - Scleroderma, Systemic

KW - Spain

KW - Sweden

KW - United Kingdom

KW - Journal Article

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/ar4124

DO - 10.1186/ar4124

M3 - Article

C2 - 23270786

SN - 1478-6354

VL - 14

SP - R273

JO - Arthritis research & therapy

JF - Arthritis research & therapy

IS - 6

ER -

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

Abstract

Keywords

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