Association of vitamin D receptor gene polymorphisms and vitamin D levels with asthma and atopy in Cypriot adolescents: a case–control study
Tóm tắt
Polymorphisms in the vitamin D receptor (VDR) gene have been studied in immune-related disorders either as independent contributors or in combination with vitamin D concentration. Vitamin D and VDR have been independently linked to asthma susceptibility. We investigated whether VDR variants were associated independently or in relation to vitamin D levels with asthma in Cypriot adolescents. We studied 190 current wheezers, 69 of which were categorized as active asthmatics and 671 healthy controls. We determined three VDR genotypes (BsmI, TaqI, ApaI) and measured serum 25(OH)D levels. Logistic regression and stratified analyses by the presence of hypovitaminosis D (≤20 ng/ml) were used to evaluate the association of the VDR variants with asthma. The distribution of TaqI genotypes was significantly different between controls and current wheezers (p = 0.030) or active asthmatics (p = 0.014). The tt genotype was over-represented in wheezers (19.2 %) and asthmatics (21.3 %) compared to respective controls (12.9 %). No difference was observed between controls, current wheezers and active asthmatics in the genotypic distribution of BsmI and ApaI polymorphic sites. After stratification by the presence of hypovitaminosis D, a significant association was detected between tt genotype of TaqI polymorphism with wheezing (OR: 1.97, 95 % CI: 1.12, 3.46) and asthma (OR: 2.37, 95CI%: 1.02, 5.52) only in those with normal vitamin D levels (>20 ng/ml) but not in subjects with low vitamin D. The minor TaqI genotype of VDR is associated with asthma in Cypriot adolescents. This polymorphism may contribute to asthma susceptibility primarily under conditions of normal vitamin D levels (>20 ng/ml).
Tài liệu tham khảo
Bener A, Ehlayel MS, Tulic MK, Hamid Q. Vitamin D deficiency as a strong predictor of asthma in children. Int Arch Allergy Immunol. 2012;157:168–75.
Checkley W, Robinson CL, Baumann LM, Hansel NN, Romero KM, Pollard SL, et al. 25-hydroxy vitamin D levels are associated with childhood asthma in a population-based study in Peru. Clin Exp Allergy. 2015;45:273–82.
Niruban SJ, Alagiakrishnan K, Beach J, Senthilselvan A. Association of vitamin D with respiratory outcomes in Canadian children. Eur J Clin Nutr. 2014;68:1334–40.
van Oeffelen AA, Bekkers MB, Smit HA, Kerkhof M, Koppelman GH, Haveman-Nies A, et al. Serum micronutrient concentrations and childhood asthma: the PIAMA birth cohort study. Pediatr Allergy Immunol. 2011;22:784–93.
Hollams EM, Hart PH, Holt BJ, Serralha M, Parsons F, de Klerk NH, et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur Respir J. 2011;38:1320–7.
Brehm JM, Acosta-Perez E, Klei L, Roeder K, Barmada M, Boutaoui N, et al. Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children. Am J Respir Crit Care Med. 2012;186:140–6.
Uysalol M, Mutlu LC, Saracoglu GV, Karasu E, Guzel S, Kayaoglu S, et al. Childhood asthma and vitamin d deficiency in Turkey: is there cause and effect relationship between them? Ital J Pediatr. 2013;39:78.
Kolokotroni O, Papadopoulou A, Middleton N, Kouta C, Raftopoulos V, Nicolaidou P, et al. Vitamin D levels and status amongst asthmatic and non-asthmatic adolescents in Cyprus: a comparative cross-sectional study. BMC Public Health. 2015;15:48.
Tolppanen AM, Sayers A, Granell R, Fraser WD, Henderson J, Lawlor DA. Prospective association of 25-hydroxyvitamin D3 and D2 with childhood lung function, asthma, wheezing, and flexural dermatitis. Epidemiology. 2013;24:310–9.
Yao TC, Tu YL, Chang SW, Tsai HJ, Gu PW, Ning HC, et al. Suboptimal vitamin D status in a population-based study of Asian children: prevalence and relation to allergic diseases and atopy. PLoS One. 2014;9:e99105.
Bosse Y, Maghni K, Hudson TJ. 1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes. Physiol Genomics. 2007;29:161–8.
Krobtrakulchai W, Praikanahok J, Visitsunthorn N, Vichyanond P, Manonukul K, Pratumvinit B, et al. The effect of vitamin D status on pediatric asthma at a university hospital, Thailand. Allergy Asthma Immunol Res. 2013;5:289–94.
Tolppanen AM, Williams D, Henderson J, Lawlor DA. Serum 25-hydroxy-vitamin D and ionised calcium in relation to lung function and allergen skin tests. Eur J Clin Nutr. 2011;65:493–500.
Haussler MR, Jurutka PW, Hsieh JC, Thompson PD, Selznick SH, Haussler CA, et al. New understanding of the molecular mechanism of receptor-mediated genomic actions of the vitamin D hormone. Bone. 1995;17:33S–8.
Wang TT, Tavera-Mendoza LE, Laperriere D, Libby E, MacLeod NB, Nagai Y, et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005;19:2685–95.
Walters MR. Newly identified actions of the vitamin D endocrine system. Endocr Rev. 1992;13:719–64.
Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008;29:361–8.
Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, et al. The nonskeletal effects of vitamin D: an endocrine society scientific statement. Endocr Rev. 2012;33:456–92.
Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality–a review of recent evidence. Autoimmun Rev. 2013;12:976–89.
Cantorna MT, Woodward WD, Hayes CE, DeLuca HF. 1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines tgf-beta 1 and IL-4. J Immunol. 1998;160:5314–9.
van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005;97:93–101.
Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A. 1alpha,25-dihydroxyvitamin D3 has a direct effect on naive CD4(+) t cells to enhance the development of Th2 cells. J Immunol. 2001;167:4974–80.
Vasiliou JE, Lui S, Walker SA, Chohan V, Xystrakis E, Bush A, et al. Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease. Allergy. 2014;69:1380–9.
Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab. 2008;4:80–90.
Adams JS, Sharma OP, Gacad MA, Singer FR. Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis. J Clin Invest. 1983;72:1856–60.
Adorini L, Penna G, Giarratana N, Roncari A, Amuchastegui S, Daniel KC, et al. Dendritic cells as key targets for immunomodulation by vitamin D receptor ligands. J Steroid Biochem Mol Biol. 2004;89–90:437–41.
Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983;221:1181–3.
Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol. 2008;181:7090–9.
Damera G, Fogle HW, Lim P, Goncharova EA, Zhao H, Banerjee A, et al. Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1. Br J Pharmacol. 2009;158:1429–41.
Saadi A, Gao G, Li H, Wei C, Gong Y, Liu Q. Association study between vitamin D receptor gene polymorphisms and asthma in the Chinese Han population: a case-control study. BMC Med Genet. 2009;10:71.
Raby BA, Lazarus R, Silverman EK, Lake S, Lange C, Wjst M, et al. Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am J Respir Crit Care Med. 2004;170:1057–65.
Poon AH, Laprise C, Lemire M, Montpetit A, Sinnett D, Schurr E, et al. Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Am J Respir Crit Care Med. 2004;170:967–73.
Ismail MF, Elnady HG, Fouda EM. Genetic variants in vitamin D pathway in Egyptian asthmatic children: a pilot study. Hum Immunol. 2013;74:1659–64.
Maalmi H, Sassi FH, Berraies A, Ammar J, Hamzaoui K, Hamzaoui A. Association of vitamin D receptor gene polymorphisms with susceptibility to asthma in Tunisian children: a case control study. Hum Immunol. 2013;74:234–40.
Pillai DK, Iqbal SF, Benton AS, Lerner J, Wiles A, Foerster M, et al. Associations between genetic variants in vitamin D metabolism and asthma characteristics in young African Americans: a pilot study. J Investig Med. 2011;59:938–46.
Fang WL, Gao LB, Liang WB, Xue H, Bai P, Lv ML, et al. Association analysis of vitamin D receptor gene polymorphisms in Chinese population with asthma. Iran J Allergy Asthma Immunol. 2009;8:141–7.
Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338:143–56.
Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, et al. Prediction of bone density from vitamin D receptor alleles. Nature. 1994;367:284–7.
Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, et al. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol. 2001;177:145–59.
Vollmert C, Illig T, Altmuller J, Klugbauer S, Loesgen S, Dumitrescu L, et al. Single nucleotide polymorphism screening and association analysis–exclusion of integrin beta 7 and vitamin D receptor (chromosome 12q) as candidate genes for asthma. Clin Exp Allergy. 2004;34:1841–50.
Tizaoui K, Berraies A, Hamdi B, Kaabachi W, Hamzaoui K, Hamzaoui A. Association of vitamin D receptor gene polymorphisms with asthma risk: systematic review and updated meta-analysis of case-control studies. Lung. 2014;192:955–65.
Li K, Shi Q, Yang L, Li X, Liu L, Wang L, et al. The association of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels with generalized vitiligo. Br J Dermatol. 2012;167:815–21.
Li H, Stampfer MJ, Hollis JB, Mucci LA, Gaziano JM, Hunter D, et al. A prospective study of plasma vitamin D metabolites, vitamin D receptor polymorphisms, and prostate cancer. PLoS Med. 2007;4:e103.
Mikhak B, Hunter DJ, Spiegelman D, Platz EA, Hollis BW, Giovannucci E. Vitamin d receptor (vdr) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Prostate. 2007;67:911–23.
Kim HS, Newcomb PA, Ulrich CM, Keener CL, Bigler J, Farin FM, et al. Vitamin D receptor polymorphism and the risk of colorectal adenomas: evidence of interaction with dietary vitamin D and calcium. Cancer Epidemiol Biomarkers Prev. 2001;10:869–74.
Yiallouros PK, Savva SC, Kolokotroni O, Behbod B, Zeniou M, Economou M, et al. Low serum high-density lipoprotein cholesterol in childhood is associated with adolescent asthma. Clin Exp Allergy. 2012;42:423–32.
Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012;67:18–24.
Li F, Jiang L, Willis-Owen SA, Zhang Y, Gao J. Vitamin D binding protein variants associate with asthma susceptibility in the Chinese Han population. BMC Med Genet. 2011;12:103.
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the institute of medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–8.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.
Heaney RP. Health is better at serum 25(OH)D above 30 ng/ml. J Steroid Biochem Mol Biol. 2013;136:224–8.
Simpson A, John SL, Jury F, Niven R, Woodcock A, Ollier WE, et al. Endotoxin exposure, CD14, and allergic disease: an interaction between genes and the environment. Am J Respir Crit Care Med. 2006;174:386–92.
Colilla S, Nicolae D, Pluzhnikov A, Blumenthal MN, Beaty TH, Bleecker ER, et al. Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure. J Allergy Clin Immunol. 2003;111:840–6.
Bodiwala D, Luscombe CJ, French ME, Liu S, Saxby MF, Jones PW, et al. Polymorphisms in the vitamin d receptor gene, ultraviolet radiation, and susceptibility to prostate cancer. Environ Mol Mutagen. 2004;43:121–7.
John EM, Schwartz GG, Koo J, Van Den Berg D, Ingles SA. Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced prostate cancer. Cancer Res. 2005;65:5470–9.