Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV 1 in the Framingham Heart Study

Respiratory Research

Patricia A Cassano^1,12  SUNLIGHT Consortium⁵  SL Booth^1,11  BM Psaty^1,13  SR Heckbert^1,10  M Fornage⁷  LJ Palmer^1,14  SA Gharib⁸  A Sood⁶  M Kowgier³  W Tang²  GT O’Connor⁴  J Dupuis⁹  W Gao¹  JG Hansen² 

[1] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA;Division of Nutritional Sciences, Cornell University, 209 Savage Hall, Ithaca 14853, NY, USA;Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada;Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA;The SUNLIGHT Consortium (Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits), ᅟ, ᅟ;University of New Mexico, Albuquerque, NM, USA;Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA;Computational Medicine Core, Center for Lung Biology, Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA, USA;The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA;Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA;Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA;Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, USA;Department of Medicine, University of Washington, Seattle, WA, USA;School of Public Health, University of Adelaide, Adelaide, Australia

关键词: Framingham Heart Study;    Lung function;    CYP2R1;    FEV1;    25-hydroxyvitamin D;    Vitamin D;   

Others  :  1233536
DOI  :  10.1186/s12931-015-0238-y

 received in 2014-12-11, accepted in 2015-06-15,  发布年份 2015

【 摘 要 】

Background

Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.

Methods

We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV ₁ ) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV ₁in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV ₁in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.

Results

We found a positive cross-sectional association between 25(OH)D and FEV ₁in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV ₁in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV ₁(gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV ₁in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).

Conclusions

Serum 25(OH)D status was associated with cross-sectional FEV ₁ , but not longitudinal change in FEV ₁ . The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV ₁and is a promising candidate gene for further studies.

【 授权许可】

   
2015 Hansen et al.

【 图 表 】

Fig. 1.

Fig. 1.

【 参考文献 】

• [1]Minino AM. Death in the United States. NCHS Data Brief. 2011; 2009:1-8.
• [2]Holick MF. Vitamin D, deficiency. N Engl J Med. 2007; 357:266-81.
• [3]Ross AC. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium.: Dietary reference intakes for calcium and vitamin D. National Academies Press, Washington, DC; 2011.
• [4]Looker AC, Johnson CL, Lacher DA, Pfeiffer CM, Schleicher RL, Sempos CT. Vitamin D Status: United States, 2001–2006. NCHS data brief, no 5. National Center for Health Statistic, Hyattsville; 2011.
• [5]Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L et al.. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010; 19:2739-45.
• [6]Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D et al.. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010; 376:180-8.
• [7]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.
• [8]Bikle DD. Vitamin D, regulation of immune function. Vitam Horm. 2011; 86:1-21.
• [9]Hansdottir S, Monick MM. Vitamin D effects on lung immunity and respiratory diseases. Vitam Horm. 2011; 86:217-37.
• [10]Pfeffer PE, Hawrylowicz CM. Vitamin D and lung disease. Thorax. 2012; 67:1018-20.
• [11]Black PN, Scragg R. Relationship between serum 25-hydroxyvitamin d and pulmonary function in the third national health and nutrition examination survey. Chest. 2005; 128:3792-8.
• [12]Choi CJSM, Choi WS, Kim KS, Youn SA, Lindsey T, Choi YJ et al.. Relationship Between Serum 25-Hydroxyvitamin D and Lung Function Among Korean Adults in Korea National Health and Nutrition Examination Survey (KNHANES), 2008–2010. J Clin Endocrinol Metab. 2013; 98:1703-10.
• [13]Berry DJ, Hesketh K, Power C, Hypponen E. Vitamin D status has a linear association with seasonal infections and lung function in British adults. Br J Nutr. 2011; 106:1433-40.
• [14]Shaheen SO, Jameson KA, Robinson SM, Boucher BJ, Syddall HE, Aihie Sayer A et al.. Relationship of vitamin D status to adult lung function and COPD. Thorax. 2011; 66:692-8.
• [15]Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, Buysschaert I et al.. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010; 65:215-20.
• [16]Lehouck A, Mathieu C, Carremans C, Baeke F, Verhaegen J, Van Eldere J et al.. High doses of vitamin d to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2012; 156:105-14.
• [17]Ginde AA, Mansbach JM, Camargo CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009; 169:384-90.
• [18]Murdoch DR, Slow S, Chambers ST, Jennings LC, Stewart AW, Priest PC et al.. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial. JAMA. 2012; 308:1333-9.
• [19]Rees JR, Hendricks K, Barry EL, Peacock JL, Mott LA, Sandler RS et al.. Vitamin D3 supplementation and upper respiratory tract infections in a randomized, controlled trial. Clin Infect Dis. 2013; 57:1384-92.
• [20]Afzal S, Lange P, Bojesen SE, Freiberg JJ, Nordestgaard BG. Plasma 25-hydroxyvitamin D, lung function and risk of chronic obstructive pulmonary disease. Thorax. 2014; 69:24-31.
• [21]Kunisaki KM, Niewoehner DE, Singh RJ, Connett JE. Vitamin D status and longitudinal lung function decline in the Lung Health Study. Eur Respir J. 2011; 37:238-43.
• [22]Lange NE, Sparrow D, Vokonas P, Litonjua AA. Vitamin D deficiency, smoking, and lung function in the Normative Aging Study. Am J Respir Crit Care Med. 2012; 186:616-21.
• [23]Ito I, Nagai S, Hoshino Y, Muro S, Hirai T, Tsukino M et al.. Risk and severity of COPD is associated with the group-specific component of serum globulin 1 F allele. Chest. 2004; 125:63-70.
• [24]Schellenberg D, Pare PD, Weir TD, Spinelli JJ, Walker BA, Sandford AJ. Vitamin D binding protein variants and the risk of COPD. Am J Respir Crit Care Med. 1998; 157:957-61.
• [25]Wood AM, Bassford C, Webster D, Newby P, Rajesh P. Stockley RA. Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages. Thorax: Thickett DR; 2011
• [26]Horne SL, Cockcroft DW, Dosman JA. Possible protective effect against chronic obstructive airways disease by the GC2 allele. Hum Hered. 1990; 40:173-6.
• [27]Chishimba L, Thickett DR, Stockley RA, Wood AM. The vitamin D axis in the lung: a key role for vitamin D-binding protein. Thorax. 2010; 65:456-62.
• [28]Feinleib M, Kannel WB, Garrison RJ, McNamara PM, Castelli WP. The Framingham Offspring Study. Design and preliminary data. Prev Med. 1975; 4:518-25.
• [29]Splansky GL, Corey D, Yang Q, Atwood LD, Cupples LA, Benjamin EJ et al.. The Third Generation Cohort of the National Heart, Lung, and Blood Institute’s Framingham Heart Study: design, recruitment, and initial examination. Am J Epidemiol. 2007; 165:1328-35.
• [30]Artigas MS, Loth DW, Wain LV, Gharib SA, Obeidat M, Tang W, Zhai G, Zhao JH, Smith AV, Huffman JE et al.. Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nat Genet. 2011; 43:1082-1090.
• [31]Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A et al.. Standardisation of spirometry. Eur Respir J. 2005; 26:319-38.
• [32]Shea MK, Benjamin EJ, Dupuis J, Massaro JM, Jacques PF, D’Agostino RB et al.. Genetic and non-genetic correlates of vitamins K and D. Eur J Clin Nutr. 2009; 63:458-64.
• [33]Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL et al.. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes. 2010; 59:242-8.
• [34]Yetley EA, Pfeiffer CM, Schleicher RL, Phinney KW, Lacher DA, Christakos S et al.. NHANES monitoring of serum 25-hydroxyvitamin D: a roundtable summary. J Nutr. 2010; 140:2030S-45S.
• [35]Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006; 38:904-9.
• [36]Liu JZ, McRae AF, Nyholt DR, Medland SE, Wray NR, Brown KM et al.. A versatile gene-based test for genome-wide association studies. Am J Hum Genet. 2010; 87:139-45.
• [37]Ligthart L, de Vries B, Smith AV, Ikram MA, Amin N, Hottenga JJ et al.. Meta-analysis of genome-wide association for migraine in six population-based European cohorts. Eur J Hum Genet. 2011; 19:901-7.
• [38]Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci U S A. 2004; 101:7711-5.
• [39]Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G. Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am J Epidemiol. 2010; 171:903-8.
• [40]Davey Smith G, Ebrahim S. ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003; 32:1-22.