TY - JOUR
T1 - Prevalence, determinants and clinical correlates of vitamin D deficiency in patients with Chronic Obstructive Pulmonary Disease in London, UK
AU - Jolliffe, David A.
AU - James, Wai Yee
AU - Hooper, Richard L.
AU - Barnes, Neil C.
AU - Greiller, Claire L.
AU - Islam, Kamrul
AU - Bhowmik, Angshu
AU - Timms, Peter M.
AU - Rajakulasingam, Raj K.
AU - Choudhury, Aklak B.
AU - Simcock, David E.
AU - Hyppönen, Elina
AU - Walton, Robert T.
AU - Corrigan, Christopher J.
AU - Griffiths, Christopher J.
AU - Martineau, Adrian R.
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/1
Y1 - 2018/1
N2 - Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41–92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants performed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV1), % predicted forced vital capacity (FVC), the ratio of FEV1 to FVC (FEV1:FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4 nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration <50 nmol/L). Lower vitamin D status was independently associated with higher body mass index (P = 0.001), lower socio-economic position (P = 0.037), lack of vitamin D supplement consumption (P < 0.001), sampling in Winter or Spring (P for trend = 0.006) and lack of a recent sunny holiday (P = 0.002). Vitamin D deficiency associated with reduced % predicted FEV1 (P for trend = 0.060) and % predicted FVC (P for trend = 0.003), but it did not associate with FEV1:FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD.
AB - Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41–92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants performed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV1), % predicted forced vital capacity (FVC), the ratio of FEV1 to FVC (FEV1:FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4 nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration <50 nmol/L). Lower vitamin D status was independently associated with higher body mass index (P = 0.001), lower socio-economic position (P = 0.037), lack of vitamin D supplement consumption (P < 0.001), sampling in Winter or Spring (P for trend = 0.006) and lack of a recent sunny holiday (P = 0.002). Vitamin D deficiency associated with reduced % predicted FEV1 (P for trend = 0.060) and % predicted FVC (P for trend = 0.003), but it did not associate with FEV1:FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD.
KW - COPD
KW - FEV1
KW - FVC
KW - Single nucleotide polymorphism
KW - Spirometry
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=85012914310&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2017.01.019
DO - 10.1016/j.jsbmb.2017.01.019
M3 - Article
C2 - 28161533
AN - SCOPUS:85012914310
SN - 0960-0760
VL - 175
SP - 138
EP - 145
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
ER -