The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D

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The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D. / Kelly, Rachel S; Chawes, Bo L; Guo, Feng; Zhang, Li; Blighe, Kevin; Litonjua, Augusto A; Raby, Benjamin A; Levy, Bruce D; Rago, Daniela; Stokholm, Jakob; Bønnelykke, Klaus; Bisgaard, Hans; Zhou, Xiaobo; Lasky-Su, Jessica A; Weiss, Scott T.

I: The European Respiratory Journal, Bind 54, Nr. 4, 1900761, 2019.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Kelly, RS, Chawes, BL, Guo, F, Zhang, L, Blighe, K, Litonjua, AA, Raby, BA, Levy, BD, Rago, D, Stokholm, J, Bønnelykke, K, Bisgaard, H, Zhou, X, Lasky-Su, JA & Weiss, ST 2019, 'The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D', The European Respiratory Journal, bind 54, nr. 4, 1900761. https://doi.org/10.1183/13993003.00761-2019

APA

Kelly, R. S., Chawes, B. L., Guo, F., Zhang, L., Blighe, K., Litonjua, A. A., Raby, B. A., Levy, B. D., Rago, D., Stokholm, J., Bønnelykke, K., Bisgaard, H., Zhou, X., Lasky-Su, J. A., & Weiss, S. T. (2019). The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D. The European Respiratory Journal, 54(4), [1900761]. https://doi.org/10.1183/13993003.00761-2019

Vancouver

Kelly RS, Chawes BL, Guo F, Zhang L, Blighe K, Litonjua AA o.a. The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D. The European Respiratory Journal. 2019;54(4). 1900761. https://doi.org/10.1183/13993003.00761-2019

Author

Kelly, Rachel S ; Chawes, Bo L ; Guo, Feng ; Zhang, Li ; Blighe, Kevin ; Litonjua, Augusto A ; Raby, Benjamin A ; Levy, Bruce D ; Rago, Daniela ; Stokholm, Jakob ; Bønnelykke, Klaus ; Bisgaard, Hans ; Zhou, Xiaobo ; Lasky-Su, Jessica A ; Weiss, Scott T. / The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D. I: The European Respiratory Journal. 2019 ; Bind 54, Nr. 4.

Bibtex

@article{620cfd6549e04c5a806273b4296408da,

title = "The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D",

abstract = "Evidence suggests vitamin D has preventive potential in asthma; however, not all children benefit from this intervention. This study aimed to investigate whether variation in the functional 17q21 single nucleotide polymorphism rs12936231 affects the preventive potential of vitamin D against asthma.A combined secondary analysis of two randomised controlled trials of prenatal vitamin D supplementation for the prevention of asthma in offspring (Vitamin D Antenatal Asthma Reduction Trial (VDAART) and Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010)) was performed, stratifying by genotype and integrating metabolite data to explore underlying mechanisms.The protective effect of vitamin D on asthma/wheeze was evident among children with the low-risk rs12936231 GG genotype (hazard ratio (HR) 0.49, 95% CI 0.26-0.94, p=0.032) but not the high-risk CC genotype (HR 1.08, 95% CI 0.69-1.69, p=0.751). In VDAART, in the GG genotype vitamin D supplementation was associated with increased plasma levels of sphingolipids, including sphingosine-1-phosphate (β 0.022, 95% CI 0.001-0.044, p=0.038), but this was not evident with the CC genotype, known to be associated with increased expression of ORMDL3 in bronchial epithelial cells. Sphingolipid levels were associated with decreased risk of asthma/wheeze, and there was evidence of interactions between sphingolipid levels, vitamin D and genotype (p-interactionvitaminD*genotype*sphingosine-1-phosphate=0.035). In a cellular model, there was a significant difference in the induction of sphingosine-1-phosphate by vitamin D between a control human bronchial epithelial cell line and a cell line overexpressing ORMDL3 (p=0.002).Results suggest prenatal vitamin D supplementation may reduce the risk of early childhood asthma/wheeze via alterations of sphingolipid metabolism dependent on the 17q21 genotype.",

author = "Kelly, {Rachel S} and Chawes, {Bo L} and Feng Guo and Li Zhang and Kevin Blighe and Litonjua, {Augusto A} and Raby, {Benjamin A} and Levy, {Bruce D} and Daniela Rago and Jakob Stokholm and Klaus B{\o}nnelykke and Hans Bisgaard and Xiaobo Zhou and Lasky-Su, {Jessica A} and Weiss, {Scott T}",

note = "Copyright {\textcopyright}ERS 2019.",

year = "2019",

doi = "10.1183/13993003.00761-2019",

language = "English",

volume = "54",

journal = "The European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "4",

}

RIS

TY - JOUR

T1 - The role of the 17q21 genotype in the prevention of early childhood asthma and recurrent wheeze by vitamin D

AU - Kelly, Rachel S

AU - Chawes, Bo L

AU - Guo, Feng

AU - Zhang, Li

AU - Blighe, Kevin

AU - Litonjua, Augusto A

AU - Raby, Benjamin A

AU - Levy, Bruce D

AU - Rago, Daniela

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Bisgaard, Hans

AU - Zhou, Xiaobo

AU - Lasky-Su, Jessica A

AU - Weiss, Scott T

PY - 2019

Y1 - 2019

N2 - Evidence suggests vitamin D has preventive potential in asthma; however, not all children benefit from this intervention. This study aimed to investigate whether variation in the functional 17q21 single nucleotide polymorphism rs12936231 affects the preventive potential of vitamin D against asthma.A combined secondary analysis of two randomised controlled trials of prenatal vitamin D supplementation for the prevention of asthma in offspring (Vitamin D Antenatal Asthma Reduction Trial (VDAART) and Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010)) was performed, stratifying by genotype and integrating metabolite data to explore underlying mechanisms.The protective effect of vitamin D on asthma/wheeze was evident among children with the low-risk rs12936231 GG genotype (hazard ratio (HR) 0.49, 95% CI 0.26-0.94, p=0.032) but not the high-risk CC genotype (HR 1.08, 95% CI 0.69-1.69, p=0.751). In VDAART, in the GG genotype vitamin D supplementation was associated with increased plasma levels of sphingolipids, including sphingosine-1-phosphate (β 0.022, 95% CI 0.001-0.044, p=0.038), but this was not evident with the CC genotype, known to be associated with increased expression of ORMDL3 in bronchial epithelial cells. Sphingolipid levels were associated with decreased risk of asthma/wheeze, and there was evidence of interactions between sphingolipid levels, vitamin D and genotype (p-interactionvitaminD*genotype*sphingosine-1-phosphate=0.035). In a cellular model, there was a significant difference in the induction of sphingosine-1-phosphate by vitamin D between a control human bronchial epithelial cell line and a cell line overexpressing ORMDL3 (p=0.002).Results suggest prenatal vitamin D supplementation may reduce the risk of early childhood asthma/wheeze via alterations of sphingolipid metabolism dependent on the 17q21 genotype.

AB - Evidence suggests vitamin D has preventive potential in asthma; however, not all children benefit from this intervention. This study aimed to investigate whether variation in the functional 17q21 single nucleotide polymorphism rs12936231 affects the preventive potential of vitamin D against asthma.A combined secondary analysis of two randomised controlled trials of prenatal vitamin D supplementation for the prevention of asthma in offspring (Vitamin D Antenatal Asthma Reduction Trial (VDAART) and Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010)) was performed, stratifying by genotype and integrating metabolite data to explore underlying mechanisms.The protective effect of vitamin D on asthma/wheeze was evident among children with the low-risk rs12936231 GG genotype (hazard ratio (HR) 0.49, 95% CI 0.26-0.94, p=0.032) but not the high-risk CC genotype (HR 1.08, 95% CI 0.69-1.69, p=0.751). In VDAART, in the GG genotype vitamin D supplementation was associated with increased plasma levels of sphingolipids, including sphingosine-1-phosphate (β 0.022, 95% CI 0.001-0.044, p=0.038), but this was not evident with the CC genotype, known to be associated with increased expression of ORMDL3 in bronchial epithelial cells. Sphingolipid levels were associated with decreased risk of asthma/wheeze, and there was evidence of interactions between sphingolipid levels, vitamin D and genotype (p-interactionvitaminD*genotype*sphingosine-1-phosphate=0.035). In a cellular model, there was a significant difference in the induction of sphingosine-1-phosphate by vitamin D between a control human bronchial epithelial cell line and a cell line overexpressing ORMDL3 (p=0.002).Results suggest prenatal vitamin D supplementation may reduce the risk of early childhood asthma/wheeze via alterations of sphingolipid metabolism dependent on the 17q21 genotype.

U2 - 10.1183/13993003.00761-2019

DO - 10.1183/13993003.00761-2019

M3 - Journal article

C2 - 31439681

VL - 54

JO - The European Respiratory Journal

JF - The European Respiratory Journal

SN - 0903-1936

IS - 4

M1 - 1900761

ER -

ID: 236171805