Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene
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Chronic obstructive pulmonary disease
Vitamin D deficiency is highly prevalent in COPD and
correlates with variants in the vitamin D-binding gene
Wim Janssens,1 Roger Bouillon,2 Bart Claes,3 Claudia Carremans,1 An Lehouck,1
Ian Buysschaert,3 Johan Coolen,4 Chantal Mathieu,5 Marc Decramer,1
Diether Lambrechts3
See Editorial, p192 ABSTRACT Surprisingly, very few studies have assessed the
1
Respiratory Division, University Introduction Vitamin D deficiency has been associated relevance of vitamin D deficiency in COPD by
Hospital Gasthuisberg, with many chronic illnesses, but little is known about its measuring serum levels of 25-hydroxyvitamin D
Katholieke Universiteit Leuven, relationship with chronic obstructive pulmonary disease (25-OHD), which is the principal circulating
Belgium 2Clinic and Laboratory (COPD). vitamin D metabolite and recognised as the best
of Experimental Medicine and
Endocrinology, Katholieke Objectives Serum 25-hydroxyvitamin D (25-OHD) levels short-term biomarker of total exposure to vitamin
Universiteit Leuven, Belgium were measured in 414 (ex)-smokers older than 50 years D.6 Forli et al reported that in a small sample of
3
Vesalius Research Center, VIB, and the link between vitamin D status and presence of patients with advanced COPD awaiting lung
Katholieke Universiteit Leuven, COPD was assessed. The rs7041 and rs4588 variants in transplantation, the majority suffered from vitamin
Belgium 4Service of Radiology,
the vitamin D-binding gene (GC) were genotyped and D deficiency (25-OHD 50% of a community-dwelling COPD cohort of
Universiteit Leuven, Belgium Results In patients with COPD, 25-OHD levels correlated 250 patients exhibited insufficient 25-OHD levels.8
5
Vesalius Research Center, VIB, significantly with forced expiratory volume in 1 s (FEV1) Unfortunately, both studies failed to compare
Belgium (r¼0.28, pDownloaded from http://thorax.bmj.com/ on October 12, 2015 - Published by group.bmj.com
Chronic obstructive pulmonary disease
measured 25-OHD serum levels in an ambulatory population of DNA analysis
414 individuals not taking vitamin D supplements, consisting of Peripheral blood was sampled in K2EDTA plastic vacutainer
patients with COPD and healthy control subjects of similar age, tubes and, after centrifugation, germline DNA was extracted
gender distribution and smoking history. We first analysed from the precipitated leucocyte cell fraction according to
whether 25-OHD levels correlated with COPD and the severity standard procedures. Germline DNA was obtained from 404 out
thereof, and then performed a joint analysis of the rs7041 and of 414 patients (97%). All patients were of Caucasian origin and
rs4588 genotypes, 25-OHD serum levels and the risk of COPD. self-reported BelgianeFlemish origin for three generations.
Genotyping for the rs7041 and rs4588 single nucleotide poly-
morphism (SNP) genetic variants was carried out at the Vesalius
MATERIALS AND METHODS
Research Institute using the Sequenom iPLEX platform, as
Patient population
described by the manufacturer (Sequenom, San Diego, California,
All 414 individuals were prospectively recruited at the University
USA). Genotype success rates for the rs7041 and rs4588 SNPs
Hospital of Leuven (Belgium). Inclusion criteria were the
were 99.8%. No significant deviations from HardyeWeinberg
following: a smoking history of at least 15 pack-years, a minimal
equilibrium were observed.
age of 50 years and no oral supplementation with vitamin D.
Patients with symptomatic COPD were recruited during their
routine follow-up at the outpatient clinic in stable clinical Statistical analysis
condition, which means that they were receiving stable All statistical analyses were performed by SAS version 9.1
treatment and had no exacerbation 6 weeks before inclusion in (SAS Institute, Cary, North Carolina, USA). For all tests, two-
the study. Smoking controls with normal spirometry (post- sided p levelsDownloaded from http://thorax.bmj.com/ on October 12, 2015 - Published by group.bmj.com
Chronic obstructive pulmonary disease
Table 1 Baseline characteristics of the study population a GOLD stage ranging from 1 to 4 were severely vitamin D
Patients with Healthy smokers deficient (Downloaded from http://thorax.bmj.com/ on October 12, 2015 - Published by group.bmj.com
Chronic obstructive pulmonary disease
50
r = 0.28 (PDownloaded from http://thorax.bmj.com/ on October 12, 2015 - Published by group.bmj.com
Chronic obstructive pulmonary disease
Table 4 Binary logistic regression analysis to assess the association Vitamin D status measured by circulating 25-OHD reflects
between presence or absence of COPD and the rs7041 genetic variant the dynamic equilibrium between vitamin D synthesis in the
(under a recessive model of inheritance) (n¼403) skin by sun exposure, vitamin D intake via food or dietary
Risk of COPD supplements and vitamin D degradation by catabolising
Model without 25-OHD Model with 25-OHD enzymes. Up to 99% of 25-OHD is bound to plasma proteins, of
OR (CI) p Value OR (CI) p Value which >90% is bound to the specific vitamin D-binding protein
(DBP).31 Patients with COPD can be considered at high risk for
25-OHD 0.94 (0.91 to 0.96)Downloaded from http://thorax.bmj.com/ on October 12, 2015 - Published by group.bmj.com
Chronic obstructive pulmonary disease
association of rs7041 with the risk for COPD.38e40 Furthermore, 18. Sinotte M, Diorio C, Berube S, et al. Genetic polymorphisms of the vitamin D binding
since the observed association between GC genetic variants and protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women.
Am J Clin Nutr 2009;89:634e40.
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and COPD, population-based prospective follow-up studies39 proteins bind vitamin D and 25-hydroxyvitamin D. Proc Natl Acad Sci USA
and placebo-controlled intervention studies,4 which are properly 1975;72:2076e80.
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21. Quanjer PH, Tammeling GJ, Cotes JE, et al. Lung volumes and forced ventilatory
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220 Thorax 2010;65:215e220. doi:10.1136/thx.2009.120659Downloaded from http://thorax.bmj.com/ on October 12, 2015 - Published by group.bmj.com
Vitamin D deficiency is highly prevalent in
COPD and correlates with variants in the
vitamin D-binding gene
Wim Janssens, Roger Bouillon, Bart Claes, Claudia Carremans, An
Lehouck, Ian Buysschaert, Johan Coolen, Chantal Mathieu, Marc
Decramer and Diether Lambrechts
Thorax 2010 65: 215-220 originally published online December 8, 2009
doi: 10.1136/thx.2009.120659
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