Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD

Linnea Jarenbäck; Sophia Frantz; Julie Weidner; Jaro Ankerst; Ulf Nihlén; Leif Bjermer; Per Wollmer; Ellen Tufvesson

doi:10.1183/23120541.00668-2021

Figures

Tables
Supplementary Materials

Download figure
Open in new tab
Download powerpoint
FIGURE 1
Lung function in COPD patients and controls divided by single nucleotide polymorphism rs793391 genotypes (as representative for block 2). a) Forced expiratory volume in 1 s (FEV₁), b) FEV₁/forced vital capacity (FVC) ratio, c) resistance at 5 Hz (R₅) and d) reactance area (AX) are divided according to the genotype of rs793391. One-way ANOVA was used for overall comparison among the groups (*: p<0.05), followed by Bonferroni's multiple comparison test between separate groups (^#: p<0.05). Genotypes are presented with the reference/reference genotype to the left. Data are presented as box-plots showing the median within the box of 25th–75th percentile and whiskers of 5th–95th percentile.
Download figure
Open in new tab
Download powerpoint
FIGURE 2
Lung function in COPD patients and controls divided by single nucleotide polymorphism rs3864051 genotypes. a) Forced expiratory volume in 1 s (FEV₁), b) FEV₁/forced vital capacity (FVC), c) diffusing capacity of the lung for carbon monoxide (D_LCO) and d) reactance area (AX) are divided according to the genotype of rs3864051. One-way ANOVA was used for overall comparison among the groups (*: p<0.05, ***: p<0.001), followed by Bonferroni's multiple comparison test between separate groups (^#: p<0.05, ^###: p<0.001). Genotypes are presented with the reference/reference genotype to the left. Data are presented as box-plots showing the median within the box of 25th–75th percentile and whiskers of 5th–95th percentile.
Download figure
Open in new tab
Download powerpoint
FIGURE 3
Lung function in COPD patients and controls divided by single nucleotide polymorphism rs11915920 genotypes (as representative for block 1). a) Forced vital capacity (FVC), b) total lung capacity (TLC), c) alveolar volume (V_A) and d) diffusing capacity of the lung for carbon monoxide (D_LCO)/V_A are divided according to the genotype of 11915920. One-way ANOVA was used for overall comparison among the groups (*: p<0.05), followed by Bonferroni's multiple comparison test between separate groups (^#: p<0.05). Genotypes are presented with the reference/reference genotype to the left. Data are presented as box-plots showing the median within the box of 25th–75th percentile and whiskers of 5th–95th percentile.

TABLE 1

Patient characteristics and lung function

	Controls	COPD	p-value
Patients	405	154
Female/male	239/166 (59/41)	71/83 (46/54)	0.006
Age, years	62±8	66±6	<0.001
Weight, kg	77±16	77±15	0.99
Height, cm	170±9	171±9	0.025
Smoking status, never-/former/current smoker	76/145/184	5/92/57	<0.001
Smoking, pack-years	22±18	36±20	<0.001
GOLD stage 1/2/3/4	NA	23/96/31/4	NA
Lung function
FEV₁, L	2.85±0.71	1.87±0.64	<0.001
FEV₁, % pred	97±13	63±17	<0.001
FVC, L	3.40±0.85	3.19±1.02	0.023
FVC, % pred	91±12	83±19	<0.001
FEV₁/FVC	0.84±0.06	0.60±0.17	<0.001
RV, % pred	116±21	150±45	<0.001
TLC, % pred	102±11	106±17	0.003
D_LCO, % pred	93±16	66±20	<0.001
V_A, % pred	96±16	91±13	<0.001
D_LCO/V_A, % pred	97±15	72±20	<0.001
R₅, kPa·s·L⁻¹	0.31±0.11	0.41±0.17	<0.001
R₂₀, kPa·s·L⁻¹	0.24±0.08	0.28±0.09	<0.001
R₅–R₂₀, kPa·s·L⁻¹	0.07±0.05	0.13±0.10	<0.001
X₅, kPa·s·L⁻¹	−0.09±0.05	−0.18±0.13	<0.001
AX, kPa·s·L⁻¹	0.34±0.39	1.13±1.33	<0.001

Data are presented as n, n (%) or mean±sd, unless otherwise stated. Significant differences are depicted in bold. Categorical data were analysed using the Chi-squared test and numeric data were analysed with the t-test. GOLD: Global Initiative for Chronic Obstructive Lung Disease; FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity; D_LCO: diffusing lung capacity of the lung for carbon monoxide; V_A: alveolar volume; R₅: resistance at 5 Hz; R₂₀: resistance at 20 Hz; X₅: reactance at 5 Hz; AX: reactance area; NA: not applicable.

TABLE 2

Genotype frequencies in healthy and COPD groups, and associations between different genotypes of sulfatase modifying factor (SUMF1) single nucleotide polymorphisms (SNPs)^# and COPD^¶

	ref/ref				ref/var var/var		p-value	OR (95% CI)⁺
		Healthy	COPD		Healthy	COPD	p-value	OR (95% CI)⁺
rs1356229	CC	387 (96)	149 (97)	CT	16 (4)	5 (3)	0.74	1.20 (0.42–3.45)
				TT	0 (0)	0 (0)
rs308739	CC	348 (87)	136 (88)	TT	54 (13)	18 (12)	0.98	1.01 (0.56–1.82)
				AA	0 (0)	0 (0)
rs4685744	CC	109 (27)	43 (28)	CT	187 (46)	73 (47)	0.83	0.95 (0.60–1.51)
				TT	107 (27)	38 (25)	0.60	0.87 (0.51–1.47)
rs2819562	CC	87 (22)	36 (23)	CT	182 (45)	74 (48)	0.63	0.89 (0.54–1.45)
				TT	133 (33)	44 (29)	0.29	0.75 (0.44–1.28)
rs2819561	AA	87 (22)	36 (23)	AG	183 (46)	74 (48)	0.61	0.88 (0.54–1.44)
				GG	132 (33)	44 (29)	0.29	0.75 (0.44–1.29)
rs2633852	AA	85 (21)	36 (23)	AG	181 (45)	74 (48)	0.61	0.88 (0.54–1.44)
				GG	134 (34)	44 (29)	0.26	0.73 (0.43–1.26)
rs11915920	CC	111 (28)	43 (28)	CT	186 (46)	75 (49)	0.99	1.00 (0.63–1.58)
				TT	105 (26)	36 (23)	0.55	0.85 (0.50–1.45)
rs807785	CC	33 (8)	17 (11)	CT	164 (41)	70 (45)	0.88	0.95 (0.49–1.85)
				TT	206 (51)	67 (44)	0.39	0.75 (0.39–1.46)
rs3864051	CC	228 (57)	69 (45)	CT	171 (43)	74 (48)	0.13	1.36 (0.92–2.03)
				TT	2 (0.5)	11 (7)	0.001	14.22 (3.04–66.49)
rs794187	CC	163 (41)	68 (44)	CT	190 (47)	70 (46)	0.37	0.83 (0.55–1.25)
				TT	49 (12)	16 (10)	0.46	0.78 (0.41–1.50)
rs794185	TT	114 (28)	52 (34)	TC	211 (52)	76 (49)	0.15	0.73 (0.47–1.12)
				CC	78 (19)	26 (17)	0.33	0.75 (0.43–1.34)
rs2322683	CC	53 (13)	20 (13)	CT	181 (45)	56 (37)	0.51	0.81 (0.44–1.50)
				TT	169 (42)	77 (50)	0.46	1.25 (0.69–2.29)
rs793391	TT	174 (43)	81 (53)	TG	185 (46)	54 (35)	0.013	0.59 (0.39–0.89)
				GG	44 (11)	19 (12)	0.70	0.88 (0.48–1.64)
rs12634249	CC	225 (56)	96 (62)	CA	157 (39)	46 (30)	0.034	0.63 (0.42–0.97)
				AA	21 (5)	12 (8)	0.56	1.26 (0.58–2.73)
rs2819590	CC	192 (48)	91 (59)	CT	175 (44)	47 (31)	0.006	0.55 (0.36–0.84)
				TT	33 (8)	16 (10)	0.97	1.01 (0.52–1.98)
rs304092	GG	191 (47)	86 (56)	GA	176 (44)	53 (34)	0.031	0.63 (0.42–0.96)
				AA	35 (9)	15 (10)	0.88	0.95 (0.48–1.86)

Data are presented as n (%), unless otherwise stated. Significant associations are depicted in bold. ^#: SNPs are sorted according to chromosome localisation (chromosome localisation is from GRCh38.p12); ^¶: logistic regression between reference allele (ref)/ref and ref/variance allele (var) or var/var as indicated, and adjusted for age, sex and smoking status; ⁺: odds ratio of having COPD depending on allele on different SNP in SUMF1.

TABLE 3

Associations between different genotypes of sulfatase modifying factor (SUMF1) single nucleotide polymorphisms and forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio in the total study population including both COPD and control subjects

	ref/ref	ref/var	FEV₁	FVC	FEV₁/FVC
	ref/ref	var/var	FEV₁	FVC	FEV₁/FVC
rs4685744	CC	CT	0.82	0.030 B= −0.12	0.093 B=0.024
		TT	0.81	0.037 B= −0.14	0.27
rs2819562	CC	CT	0.79	0.048 B= −0.12	0.076 B=0.027
		TT	0.73	0.057 B= −0.13	0.074 B=0.030
rs2819561	AA	AG	0.76	0.050 B= −0.12	0.073 B=0.0028
		GG	0.71	0.060 B= −0.12	0.076 B=0.029
rs2633852	AA	AG	0.72	0.062 B= −0.12	0.075 B=0.028
		GG	0.67	0.071 B= −0.12	0.073 B=0.030
rs11915920	CC	CT	0.98	0.021 B= −0.13	0.15
		TT	0.84	0.031 B= −0.14	0.23
rs807785	CC	CT	0.87	0.64	0.61
		TT	0.41	0.87	0.16
rs3864051	CC	CT	0.48	0.14	0.67
		TT	<0.001 B= −0.64	0.31	<0.001 B= −0.20
rs794187	CC	CT	0.028 B=0.12	0.062 B=0.094	0.22
		TT	0.72	0.62	0.98
rs794185	TT	TC	0.002 B=0.18	0.004 B=0.16	0.11
		CC	0.033 B=0.16	0.057 B=0.13	0.32
rs2322683	CC	CT	0.17	0.25	0.41
		TT	0.87	0.57	0.82
rs793391	TT	TG	0.024 B=0.12	0.42	0.039 B=0.026
		GG	0.66	0.65	0.79
rs12634249	CC	CA	0.039 B=0.11	0.30	0.060 B=0.024
		AA	0.12	0.89	0.077 B= −0.045
rs2819590	CC	CT	0.010 B=0.14	0.36	0.016 B=0.030
		TT	0.76	0.74	0.42
rs304092	GG	GA	0.025 B=0.12	0.44	0.037 B=0.026
		AA	0.99	0.53	0.39

Data are presented as p-values from linear regression between the reference allele (ref)/ref and ref/variance allele (var) or var/var (using ref/ref as reference genotype) as indicated, and adjusted for age, sex, height and smoking status. B-value is the unstandardised β-value, and is presented when p<0.1. Significant associations are depicted in bold.

TABLE 4

Associations between different genotypes of sulfatase modifying factor (SUMF1) single nucleotide polymorphisms and diffusing capacity and lung volumes in the total study population including both COPD and control subjects

	ref/ref	ref/var	D_LCO	V_A	D_LCO/V_A	RV	TLC
	ref/ref	var/var	D_LCO	V_A	D_LCO/V_A	RV	TLC
rs4685744	CC	CT	0.26	0.23	0.080 B=0.048	0.46	0.088 B= −0.14
		TT	0.14	0.006 B= −0.22	0.0 B=0.11	0.068 B=−0,15	0.009 B= −0.25
rs2819562	CC	CT	0.12	0.41	0.023 B=0.067	0.49	0.13
		TT	0.041 B=0.38	0.083 B= −0.14	<0.001 B=0.11	0.068 B=−0.15	0.024 B= −0.22
rs2819561	AA	AG	0.12	0.41	0.023 B=0.067	0.47	0.12
		GG	0.036 B=0.39	0.090 B= −0.14	<0.001 B=0.11	0.069 B=−0.15	0.027 B= −0.21
rs2633852	AA	AG	0.12	0.40	0.022 B=0.068	0.41	0.11
		GG	0.044 B=0.38	0.099 B= −0.14	0.001 B=0.11	0.062 B= −0.15	0.025 B= −0.22
rs11915920	CC	CT	0.37	0.19	0.12	0.56	0.10 B= −0.14
		TT	0.11	0.010 B= −0.21	<0.001 B=0.11	0.059 B= −0.15	0.012 B= −0.24
rs807785	CC	CT	0.91	0.38	0.75	0.26	0.062 B= −0.24
		TT	0.72	0.87	0.67	0.18	0.23
rs3864051	CC	CT	0.12	0.057 B=0.11	0.70	0.56	0.063 B=0.13
		TT	0.029 B= −1.01	0.49	0.080 B= −0.14	0.16	0.29
rs794187	CC	CT	0.15	0.030 B=0.13	0.81	0.67	0.69
		TT	0.67	0.94	0.64	0.80	0.91
rs794185	TT	TC	0.091 B=0.26	0.001 B=0.22	0.86	0.32	0.36
		CC	0.14	0.29	0.33	0.37	0.76
rs2322683	CC	CT	0.96	0.061 B=0.17	0.35	0.66	0.22
		TT	0.82	0.50	0.49	0.91	0.26
rs793391	TT	TG	0.34	0.064 B=0.11	0.86	0.44	0.92
		GG	0.70	0.64	0.91	0.51	0.50
rs12634249	CC	CA	0.84	0.58	0.92	0.022 B= −0.14	0.29
		AA	0.18	0.73	0.25	0.27	0.81
rs2819590	CC	CT	0.32	0.078 B=0.11	0.73	0.28	0.54
		TT	0.45	0.91	0.39	0.16	0.52
rs304092	GG	GA	0.43	0.095 B=0.10	0.89	0.45	0.48
		AA	0.78	0.71	0.52	0.28	0.60

Data are presented as p-values from linear regression between the reference allele (ref)/ref and ref/variance allele (var) or var/var as indicated, and adjusted for age, sex, height and smoking status. B-value is the unstandardised β-value, and is shown when p<0.1. Significant associations are depicted in bold. D_LCO: diffusing capacity of the lung for carbon monoxide; V_A: alveolar volume; RV: residual volume; TLC: total lung capacity.

TABLE 5

Associations between different genotypes of sulfatase modifying factor (SUMF1) single nucleotide polymorphisms and airway resistance and reactance measured by impulse oscillometry in the total study population including both COPD and control subjects

	ref/ref	ref/var	R₅	R₂₀	R₅–R₂₀	X₅	AX
	ref/ref	var/var	R₅	R₂₀	R₅–R₂₀	X₅	AX
rs4685744	CC	CT	0.56	0.35	0.82	0.83	0.72
		TT	0.32	0.46	0.44	0.64	0.95
rs2819562	CC	CT	0.32	0.41	0.28	0.52	0.21
		TT	0.69	0.82	0.80	0.95	0.61
rs2819561	AA	AG	0.31	0.41	0.27	0.50	0.20
		GG	0.67	0.85	0.74	0.94	0.63
rs2633852	AA	AG	0.27	0.33	0.26	0.48	0.19
		GG	0.83	0.99	0.86	0.97	0.55
rs11915920	CC	CT	0.61	0.36	0.89	0.70	0.85
		TT	0.33	0.52	0.39	0.65	0.92
rs807785	CC	CT	0.45	0.85	0.14	0.13	0.22
		TT	0.49	0.76	0.15	0.095 B=0.022	0.26
rs3864051	CC	CT	0.29	0.45	0.39	0.21	0.36
		TT	0.032 B=0.079	0.43	0.003 B=0.062	0.005 B= −0.067	0.009 B=0.61
rs794187	CC	CT	0.086 B= −0.020	0.72	0.013 B= −0.017	0.018 B=0.018	0.015 B= −0.18
		TT	0.79	0.93	0.56	0.91	0.79
rs794185	TT	TC	0.002 B= −0.039	0.14	<0.001 B= −0.026	<0.001 B=0.030	<0.001 B= −0.30
		CC	0.030 B= −0.035	0.39	0.004 B= −0.026	0.031 B=0.023	0.020 B= −0.24
rs2322683	CC	CT	0.21	0.33	0.27	0.11	0.11
		TT	0.62	0.89	0.48	0.89	0.81
rs793391	TT	TG	0.014 B= −0.029	0.16	0.007 B= −0.018	0.012 B=0.019	0.008 B= −0.20
		GG	0.60	0.71	0.61	0.96	1.00
rs12634249	CC	CA	0.13	0.68	0.029 B= −0.014	0.024 B=0.017	0.028 B= −0.16
		AA	0.39	0.87	0.30	0.59	0.48
rs2819590	CC	CT	0.010 B= −0.030	0.048 B= −0.014	0.021 B= −0.015	0.025 B=0.17	0.011 B= −0.19
		TT	0.85	0.92	0.84	0.65	0.71
rs304092	GG	GA	0.010 B= −0.030	0.053 B= −0.014	0.018 B= −0.016	0.029 B=0.017	0.022 B= −0.17
		AA	0.81	0.78	0.92	0.69	0.66

Data are presented as p-values from linear regression between the reference allele (ref)/ref and ref/variance allele (var) or var/var, adjusted for age, sex, height and smoking status. B-value is the unstandardised β-value and is shown when p<0.1. Significant associations are depicted in bold. R₅: resistance at 5 Hz; R₂₀: resistance at 20 Hz; X₅: reactance at 5 Hz; AX: reactance area.

Supplementary Materials

Figures
Tables

Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material 00668-2021.SUPPLEMENT
Figure S1 00668-2021.FIGURES1

Vol 8 Issue 2 Table of Contents

Main menu

User menu

Search

Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD

Figures

Tables

Supplementary Materials

Supplementary Material

Citation Manager Formats

Subjects

More in this TOC Section

Original research articles

COPD

Related Articles

Contact us

Main menu

User menu

Search

Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD

Figures

Tables

Supplementary Materials

Supplementary Material

Citation Manager Formats

Jump To

Subjects

More in this TOC Section

Original research articles

COPD

Related Articles

Contact us