Relationship between vitamin D-binding protein polymorphisms and blood vitamin D level in Korean patients with COPD

Figures & data

Table 1 Baseline characteristics of the study population

Characteristics	Total participants (N=175)*
Sex, male	171 (97.7)
Age, years	66.4±6.8
Height, cm	165.4±6.2
BMI, kg/m^2	22.9±3.4
Smoking status
Current	45 (25.7)
Former	130 (74.3)
Pack-years	45.6±23.1
Underlying diseases
Coronary vascular disease	18 (10.3)
Cerebrovascular disease	7 (4.0)
Hypertension	55 (31.4)
Diabetes mellitus	19 (10.9)
Chronic kidney disease	3 (1.7)
Liver disease	7 (4.0)
Asthma	50 (28.6)
Malignancy	6 (5.1)
FEV1, L	1.51±0.51
FEV1, % predicted	57.5±18.0
FVC, L	3.16±0.84
FVC, % predicted	84.1±20.9
FEV1/FVC, %	48.0±10.6
GOLD classification
I	12 (6.9)
II	87 (49.7)
III	64 (36.6)
IV	12 (6.9)
Measured with emphysema index, % (N=131)	21.9±16.5
Measured with 6MW distance, meters (m) (N=129)	438.7±77.5
Plasma 25-hydroxyvitamin D3 level, ng/mL	17.5±9.5
VDBP variants (N=350)#
GC1F	155 (44.3)
GC1S	83 (23.7)
GC2	112 (32.0)
Genotypes (N=175)
1F-1F	35 (20.0)
1F-1S	37 (21.1)
1F-2	48 (27.4)
1S-1S	8 (4.6)
1S-2	30 (17.1)
2-2	17 (9.7)

Note:

* Data are presented as the number of patients (percentage) or mean ± standard deviation.

# Number of total variants; because there are two variants in each individual, double the number (350) of 175 is included in the analysis.

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; 6MW, 6-minute walking; VDBP, vitamin D-binding protein.

Table 2 Seasonal variation in baseline plasma vitamin D level

Note: *One-way analysis of variance was used.

Abbreviation: SD, standard deviation.

Table 3 Plasma vitamin D level according to GC variants and genotypes

Variables	Participants (N)	Vitamin D level, ng/mL*	Vitamin D deficiency#
Variant
GC1F	120	18.3±9.6	79 (65.8)
Non-GC1F	55	15.7±9.0	43 (78.2)
P-value		0.094	0.099
GC1S	75	18.3±10.7	52 (69.3)
Non-GC1S	100	16.9±8.5	70 (70.0)
P-value		0.328	0.924
GC2	95	15.5±8.8	75 (78.9)
Non-GC2	80	19.9±9.7	47 (58.8)
P-value		0.002	0.004
Genotype
1F-1F	35	18.5±7.0	20 (57.1)
Non-1F-1F	140	17.3±10.0	102 (72.9)
P-value		0.500	0.070
1F-1S	37	20.7±11.4	23 (62.2)
Non-1F-1S	138	16.7±8.8	99 (71.7)
P-value		0.021	0.260
1F-2	48	16.4±9.5	36 (75.0)
Non-1F-2	127	17.9±9.5	86 (67.7)
P-value		0.336	0.350
1S-1S	8	22.2 (11.7–33.6)	4 (50.0)
Non-1S-1S	167	15.5 (10.9–22.0)	118 (70.7)
P-value		0.189	0.246
1S-2	30	14.2±8.1	25 (83.3)
Non-1S-2	145	18.2±9.6	97 (66.9)
P-value		0.034	0.075
2-2	17	15.0 (8.1–19.9)	14 (82.4)
Non-2-2	158	15.8 (11.3–22.8)	108 (68.4)
P-value		0.164	0.233

Notes:

* Data are presented as mean ± standard deviation, median (interquartile range) or P-value.

# Data are presented as the number of patients (percentage) or P-value. Vitamin D deficiency was defined as plasma level of 25-hydroxyvitamin D₃ lower than 20 ng/mL.

Table 4 Adjusted estimates of various factors for plasma vitamin D level

	Model 1: variant GC2			Model 2: genotype 1F-1S
	Estimated	Standard error	P-value	Estimated	Standard error	P-value
Variant/genotype	−3.73	1.44	0.010	4.08	1.73	0.020
Age, years	0.06	0.11	0.589	0.07	0.11	0.525
BMI, kg/m^2	−0.07	0.23	0.781	−0.09	0.23	0.687
FEV1, % predicted	−0.04	0.05	0.463	−0.04	0.05	0.403
FEV1/FVC	0.20	0.09	0.029	0.25	0.09	0.005
Smoking status	−2.71	1.64	0.099	−2.39	1.65	0.149
Smoking, pack-years	0.05	0.03	0.096	0.06	0.03	0.061
Seasonal variation in plasma vitamin D level	0.10	0.78	0.901	0.04	0.79	0.957

Abbreviations: BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 1 Risk of vitamin D deficiency in COPD patients with various GC polymorphisms.

Notes: (A) Three different variants; (B) six different genotypes. Data are presented as odds ratio and 95% confidence interval for each GC variant and genotype.

Table 5 Adjusted estimates of VDBP variants/genotypes and vitamin D deficiency* for FEV₁/FVC, 6MW distance, and emphysema index

Models	FEV1/FVC#			6MW distance†			Emphysema index^
	Estimated	SE	P-value	Estimated	SE	P-value	Estimated	SE	P-value
Model 1
Variant GC1F	−1.35	1.33	0.309	−38.91	14.54	0.009	–	–	–
Vitamin D deficiency	−3.39	1.34	0.013	−33.57	15.17	0.029
Model 2
Variant GC1S	−0.75	1.24	0.547	–	–	–	6.56	2.85	0.023
Vitamin D deficiency	−3.26	1.34	0.016				1.78	3.37	0.599
Model 3
Variant GC2	−2.46	1.25	0.050	26.98	12.83	0.038	–	–	–
Vitamin D deficiency	−2.67	1.36	0.051	−35.46	15.60	0.025
Model 4
Genotype 1F-1F	3.61	1.52	0.018	−19.42	16.57	0.244	–	–	–
Vitamin D deficiency	−2.85	1.33	0.034	−31.47	15.68	0.048
Model 5
Genotype 1F-1S	−1.20	1.51	0.428	−24.60	15.01	0.105	9.86	3.20	0.003
Vitamin D deficiency	−3.34	1.34	0.014	−31.05	15.48	0.048	2.10	3.31	0.528
Model 6
Genotype 1F-2	−3.31	1.35	0.015	–	–	–	–	–	–
Vitamin D deficiency	−2.97	1.32	0.026
Model 7
Genotype 1S-1S	4.66	2.90	0.110	–	–	–	−13.11	6.00	0.031
Vitamin D deficiency	−3.05	1.34	0.023				0.90	3.38	0.790
Model 8
Genotype 1S-2	−1.35	1.63	0.408	–	–	–	–	–	–
Vitamin D deficiency	−3.11	1.35	0.022
Model 9
Genotype 2-2	3.13	2.06	0.131	41.84	24.23	0.088	–	–	–
Vitamin D deficiency	−3.41	1.34	0.012	−33.71	15.65	0.034

Notes:

* Vitamin D deficiency was defined as plasma level of 25-hydroxyvitamin D₃ lower than 20 ng/mL.

# Adjusted for age, BMI, smoking status (former or current smoker), pack-years, seasonal variation in plasma vitamin D level, and FEV₁ % predicted (N=174).

† Adjusted for age, BMI, smoking status (former or current smoker), pack-years, seasonal variation in plasma vitamin D level, FEV₁ % predicted, and FEV₁/FVC (N=129).

^ Adjusted for age, BMI, smoking status (former or current smoker), pack-years, seasonal variation in plasma vitamin D level, FEV₁ % predicted, and FEV₁/FVC (N=131). ‘−’ represents data that were statistically not significant.

Abbreviations: VDBP, vitamin D-binding protein; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; 6MW, 6-minute walking; SE, standard error; BMI, body mass index.