Sage Journals: Discover world-class research

Abstract

This study was aimed at investigating the correlation between genetic polymorphisms relevant to metabolic pathway of vitamin D3 (VD₃) and susceptibility to childhood bronchial asthma. Altogether 143 childhood patients with bronchial asthma and 143 healthy children of Chinese Han ethnicity were enrolled in this study. The key single-nucleotide polymorphisms (SNPs) were identified by HaploView 4.2 software and selected from previous investigations. Genomic DNAs were isolated from peripheral blood samples by using TaqMan Blood DNA kits. The genotyping of SNPs was performed by TaqMan SNPs genotyping assay. Odds ratios and corresponding 95% confidence intervals were calculated to evaluate the association between SNPs and susceptibility to bronchial asthma. Statistical analyses were conducted by using SPSS 13.0 software. Rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR were shown to be significantly associated with increased risk of bronchial asthma. Besides, prognosis of childhood bronchial asthma, which was represented as Saint George Respiratory Questionnaire (SGRQ) scoring, was closely linked with CYP2R1 rs10766197, CYP27B1 rs4646536, VDR rs7975232, VDR rs1544410, PPAR rs1805192, and PPAR rs10865710. The haplotype analysis suggested that TA and CG of CG rs7041/rs4588, CA and AG of VDR rs7975232/rs1544410, and CC of PPAR rs1805192/rs10865710 were, respectively, correlated with levels of VD, IL-4, and IL-5. And only haplotypes of VDR showed associations with risk of bronchial asthma during childhood, whereas hardly any significance could be observed between the haplotypes and behavior of quality-of-life (SGRQ) scoring. Significant associations were found between rs10766197 of CYP2R1, rs7041 and rs4588 of CG, rs4646536 of CYP27B1, rs2228570, rs7975232, and rs1544410 of VDR, as well as rs1805192 and rs10865710 of PPAR and susceptibility to and prognosis of childhood bronchial asthma, providing novel targets for treating the disorder.

Get full access to this article

View all access options for this article.

References

Baumgartner

, Mensink

R.P.

, Smet

, Konings

, Fuentes

, de Vos

W.M.

, et al. (2017). Effects of plant stanol ester consumption on fasting plasma oxy(phyto)sterol concentrations as related to fecal microbiota characteristics. J Steroid Biochem Mol Biol, 169, 46–53.

Berndt

, Savage

H.S.

, Stearns

T.M.

, and Paigen

(2011). Genetic analysis of lung function in inbred mice suggests vitamin D receptor as a candidate gene. Mol Genet Genomics, 286, 237–246.

Bosse

, Maghni

, and Hudson

T.J.

(2007). 1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes. Physiol Genomics, 29, 161–168.

Brehm

J.M.

, Celedon

J.C.

, Soto-Quiros

M.E.

, Avila

, Hunninghake

G.M.

, Forno

, et al. (2009). Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med, 179, 765–771.

Centers for Disease Control and Prevention. (2011). Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001–2009. MMWR Morb Mortal Wkly Rep, 60, 547–552.

Chinellato

, Piazza

, Sandri

, Peroni

D.G.

, Cardinale

, Piacentini

G.L.

, et al. (2011). Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma. Eur Resp J, 37, 1366–1370.

Cooper

M.A.

, Fehniger

T.A.

, and Caligiuri

M.A.

(2001). The biology of human natural killer-cell subsets. Trends Immunol, 22, 633–640.

Dai

, Sayama

, Tohyama

, Shirakata

, Hanakawa

, Tokumaru

, et al. (2010). PPARgamma mediates innate immunity by regulating the 1alpha,25-dihydroxyvitamin D3 induced hBD-3 and cathelicidin in human keratinocytes. J Dermatol Sci, 60, 179–186.

De Fabo

E.C.

(2006). Initial studies on an in vivo action spectrum for melanoma induction. Prog Biophys Mol Biol, 92, 97–104.

10.

Flugge

, Krusekopf

, Goldammer

, Osswald

, Terhalle

, Malzahn

, et al. (2007). Vitamin D receptor haplotypes protect against development of colorectal cancer. Eur J Clin Pharmacol, 63, 997–1005.

11.

Ginde

A.A.

, Mansbach

J.M.

, and Camargo

C.A.

Jr . (2009). Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med, 169, 384–390.

12.

Hashimoto

, and Nakahara

(2002). Improvement of asthma after administration of pioglitazone. Diabetes Care 25, 401.

13.

Hayes

C.E.

, Nashold

F.E.

, Spach

K.M.

, and Pedersen

L.B.

(2003). The immunological functions of the vitamin D endocrine system. Cell Mol Biol, 49, 277–300.

14.

Hida

, Kawada

, Kayahashi

, Ishihara

, and Fushiki

(1998). Counteraction of retinoic acid and 1,25-dihydroxyvitamin D3 on up-regulation of adipocyte differentiation with PPARgamma ligand, an antidiabetic thiazolidinedione, in 3T3-L1 cells. Life Sci, 62, PL205–PL211.

15.

Holgate

S.T.

(2012). Innate and adaptive immune responses in asthma. Nat Med, 18, 673–683.

16.

Ingles

S.A.

, Haile

R.W.

, Henderson

B.E.

, Kolonel

L.N.

, Nakaichi

, Shi

C.Y.

, et al. (1997). Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies. Cancer Epidemiol Biomarkers Prev, 6, 93–98.

17.

, Jiang

, Willis-Owen

S.A.

, Zhang

, and Gao

(2011). Vitamin D binding protein variants associate with asthma susceptibility in the Chinese Han population. BMC Med Genet 12, 103.

18.

, Dai

, Sun

, Zhang

, Jiang

, Ma

, et al. (2015). Association of peroxisome proliferator-activated receptor-gamma gene polymorphisms and gene-gene interaction with asthma risk in a Chinese adults population. Int J Clin Exp Med, 8, 19346–19352.

19.

Maalmi

, Sassi

F.H.

, Berraies

, Ammar

, Hamzaoui

, and Hamzaoui

(2013). Association of vitamin D receptor gene polymorphisms with susceptibility to asthma in Tunisian children: a case control study. Hum Immunol, 74, 234–240.

20.

Mak

, and Hanania

N.A.

(2011). Vitamin D and asthma. Curr Opin Pulm Med, 17, 1–5.

21.

Maria

S.P.J.

, Ramos

Gonzalez

, J., Ignacio

C.A.J.

, Maria

M.N.A.

, and Pedro

G.G.F.

(2010). The health-related quality of life of patients with chronic obstructive pulmonary disease and asthma evaluated by the SGRQ. Rev Port Pneumol, 16, 543–558.

22.

Matheu

, Back

, Mondoc

, and Issazadeh-Navikas

(2003). Dual effects of vitamin D-induced alteration of TH1/TH2 cytokine expression: enhancing IgE production and decreasing airway eosinophilia in murine allergic airway disease. J Allergy Clin Immunol, 112, 585–592.

23.

Moorman

J.E.

, Zahran

, Truman

B.I.

, Molla

M.T.

; Centers for Disease Control and Prevention (CDC). (2011). Current asthma prevalence—United States, 2006–2008. MMWR Suppl 60, 84–86.

24.

Papadopoulou

, Kouis

, Middleton

, Kolokotroni

, Karpathios

, Nicolaidou

, et al. (2015). Association of vitamin D receptor gene polymorphisms and vitamin D levels with asthma and atopy in Cypriot adolescents: a case-control study. Multidiscip Respir Med 10, 26.

25.

Park

S.J.

, and Lee

Y.C.

(2008). Peroxisome proliferator-activated receptor gamma as a novel therapeutic target in asthma. J Asthma, 45, 1–8.

26.

Paul

, Brehm

J.M.

, Alcorn

J.F.

, Holguin

, Aujla

S.J.

, and Celedon

J.C.

(2012). Vitamin D and asthma. Am J Resp Crit Care Med, 185, 124–132.

27.

Raby

B.A.

, Lazarus

, Silverman

E.K.

, Lake

, Lange

, Wjst

, et al. (2004). Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am J Resp Crit Care Med, 170, 1057–1065.

28.

Sertznig

, Seifert

, Tilgen

, and Reichrath

(2009). Activation of vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)(2)D(3) in melanoma cell lines and other skin-derived cell lines. Dermatoendocrinology, 1, 232–238.

29.

Sharief

, Jariwala

, Kumar

, Muntner

, and Melamed

M.L.

(2011). Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol, 127, 1195–1202.

30.

Shuhua

, Yanyan

, Qing

, Lingai

, Qingjuan

, Jinying

, et al. (2010). The Logistic regression analysis on related factors of asthmatic children. J Clin Pediatr, 28, 455–458.

31.

Slominski

A.T.

, Kim

T.K.

, Hobrath

J.V.

, Oak

A.S.W.

, Tang

E.K.Y.

, Tieu

E.W.

, et al. (2016). Endogenously produced nonclassical vitamin D hydroxy-metabolites act as “biased” agonists on VDR and inverse agonists on RORalpha and RORgamma. J Steroid Biochem Mol Biol. http://dx.doi.org/10.1016/j.jsbmb.2016.09.024

32.

Slominski

A.T.

, Kim

T.K.

, Li

, Postlethwaite

, Tieu

E.W.

, Tang

E.K.

, et al. (2015a). Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland. Sci Rep 5, 14875.

33.

Slominski

A.T.

, Kim

T.K.

, Shehabi

H.Z.

, Semak

, Tang

E.K.

, Nguyen

M.N.

, et al. (2012). In vivo evidence for a novel pathway of vitamin D(3) metabolism initiated by P450scc and modified by CYP27B1. FASEB J, 26, 3901–3915.

34.

Slominski

A.T.

, Kim

T.K.

, Shehabi

H.Z.

, Tang

E.K.

, Benson

H.A.

, Semak

, et al. (2014a) In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland. Mol Cell Endocrinol, 383, 181–192.

35.

Slominski

A.T.

, Kim

T.K.

, Takeda

, Janjetovic

, Brozyna

A.A.

, Skobowiat

, et al. (2014b). RORalpha and ROR gamma are expressed in human skin and serve as receptors for endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D. FASEB J, 28, 2775–2789.

36.

Slominski

A.T.

, Li

, Kim

T.K.

, Semak

, Wang

, Zjawiony

J.K.

, et al. (2015b). Novel activities of CYP11A1 and their potential physiological significance. J Steroid Biochem Mol Biol, 151, 25–37.

37.

Sun

(2010). Vitamin D and mucosal immune function. Curr Opin Gastroenterol, 26, 591–595.

38.

Tse

, and Horner

A.A.

(2008). Allergen tolerance versus the allergic march: the hygiene hypothesis revisited. Curr Allergy Asthma Rep, 8, 475–483.

39.

Urashima

, Segawa

, Okazaki

, Kurihara

, Wada

, and Ida

(2010). Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr, 91, 1255–1260.

40.

Wjst

(2005). Variants in the vitamin D receptor gene and asthma. BMC Genetics 6, 2.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB

Associations of Genetic Polymorphisms Relevant to Metabolic Pathway of Vitamin D3 with Development and Prognosis of Childhood Bronchial Asthma

Abstract

Get full access to this article

References

Supplementary Material