Gene–Gene Interactions Between Glutathione S-Transferase M1 and Matrix Metalloproteinases 1, 9, and 12 in Chronic Obstructive Pulmonary Disease in Serbians

Figures & data

Table 1. Distribution of MMP1, MMP9, and MMP12 Gene Variants in COPD Patients and Controls.

Gene, reference SNP ID number	Genotype, allele	COPD, % (N = 122)	Controls, % (N = 100)	p, OR (95.5% CI)^a	p, OR (95.5% CI)^b
MMP1 rs1799750	G/G	23.8	31.0	1	1
	G/GG	46.7	51.0	0.581, 1.19 (0.63–2.25)	0.598, 1.21 (0.60–2.45)
	GG/GG	29.5	18.0	0.049, 2.14 (1.00–4.57)	0.036, 2.50 (1.06–5.91)
	GG	52.9	43.5	0.049, 1.46 (1.00–2.12)	0.037, 1.57 (1.03–2.40)
MMP9 rs3918242	C/C	67.2	72.0	1	1
	C/T	31.2	24.0	0.283, 1.39 (0.76–2.54)	0.296, 1.43 (0.73–2.82)
	T/T	1.6	4.0	0.350, 0.44 (0.08–2.47)	0.894, 0.87 (0.11–6.63)
	T	17.2	16.0	0.733, 1.09 (0.66–1.81)	0.438, 1.25 (0.71–2.23)
MMP12 rs2276109	A/A	82.0	73.0	1	1
	A/G	15.6	24.0	0.110, 0.58 (0.29–1.13)	0.094, 0.53 (0.25–1.11)
	G/G	2.4	3.0	0.705, 0.73 (0.14–3.72)	0.612, 0.60 (0.09–4.23)
	G	10.2	15.0	0.132, 0.65 (0.37–1.14)	0.100, 0.59 (0.31–1.11)

COPD, chronic obstructive pulmonary disease; MMP, matrix metalloproteinase; and SNP, single nucleotide polymorphism.

^a Crude.

^b Adjusted for age, gender, and smoking status.

Table 2. Gene–Gene Interactions Between GSTs M1, T1, and P1 and MMPs 1, 9, and 12 in COPD.

Gene–gene interaction	Genotype	COPD, % (N = 122)	Controls, % (N = 100)	p, OR (95.5% CI)^a	p, OR (95.5% CI)^b
GSTM1-MMP1	wt-G/G	9.0	19.0	1	1
	null-G/G	14.8	13.0	0.097, 2.39 (0.85–6.70)	0.210, 2.08 (0.66–6.51)
	wt-GG/	29.5	34.0	0.178, 1.83 (0.76–4.40)	0.186, 1.96 (0.72–5.30)
	null-GG/	46.7	34.0	0.015, 2.90 (1.23–6.81)	0.028, 2.99 (1.12–7.97)
GSTT1-MMP1	wt-G/G	18.0	25.0	1	1
	null-G/G	5.8	7.0	0.834, 1.14 (0.34–3.75)	0.666, 1.35 (0.35–5.18)
	wt-GG/	59.8	51.0	0.158, 1.63 (0.83–3.20)	0.107, 1.86 (0.87–3.96)
	null-GG/	16.4	17.0	0.510, 1.34 (0.56–3.17)	0.397, 1.53 (0.57–4.14)
GSTP1-MMP1	Ile/Ile-G/G	9.0	13.0	1	1
	Val/-G/G	14.8	19.0	0.830, 1.12 (0.40–3.13)	0.683, 0.79 (0.25–2.50)
	Ile/Ile-GG/	30.3	32.0	0.511, 1.37 (0.54–3.47)	0.847, 1.11 (0.39–3.12)
	Val/-GG/	45.9	36.0	0.188, 1.84 (0.74–4.55)	0.258, 1.79 (0.65–4.93)
GSTM1-MMP9	wt-C/C	28.7	38.0	1	1
	null-C/C	38.5	34.0	0.211, 1.50 (0.79–2.84)	0.254, 1.52 (0.74–3.13)
	wt-T/	9.8	15.0	0.756, 0.87 (0.36–2.11)	0.782, 1.15 (0.42–3.12)
	null-T/	23.0	13.0	0.038, 2.34 (1.05–5.22)	0.072, 2.29 (0.93–5.63)
GSTT1-MMP9	wt-C/C	52.5	56.0	1	1
	null-C/C	14.7	16.0	0.968, 0.98 (0.46–2.11)	0.804, 1.12 (0.46–2.70)
	wt-T/	25.4	20.0	0.370, 1.36 (0.70–2.64)	0.247, 1.57 (0.73–3.35)
	null-T/	7.4	8.0	0.976, 0.98 (0.36–2.72)	0.942, 1.04 (0.32–3.40)
GSTP1-MMP9	Ile/Ile-C/C	24.6	32.0	1	1
	Val/-C/C	42.6	40.0	0.322, 1.39 (0.73–2.65)	0.771, 1.11 (0.53–2.32)
	Ile/Ile-T/	14.8	13.0	0.380, 1.48 (0.62–3.52)	0.945, 1.03 (0.39–2.71)
	Val/-T/	18.0	15.0	0.287, 1.56 (0.69–3.57)	0.134, 2.11 (0.79–5.63)
GSTM1-MMP12	wt-G/	5.7	17.0	1	1
	null-G/	12.3	10.0	0.033, 3.64 (1.11–11.97)	0.129, 2.73 (0.75–9.95)
	wt-A/A	32.8	36.0	0.049, 2.70 (1.00–7.25)	0.083, 2.66 (0.88–8.02)
	null-A/A	49.2	37.0	0.006, 3.94 (1.49–10.40)	0.015, 3.82 (1.29–11.33)
GSTT1-MMP12	wt-G/	11.5	20.0	1	1
	null-G/	6.5	7.0	0.432, 1.63 (0.48–5.55)	0.573, 1.51 (0.36–6.25)
	wt-A/A	66.4	56.0	0.062, 2.07 (0.96–4.43)	0.074, 2.17 (0.93–5.06)
	null-A/A	15.6	17.0	0.332, 1.60 (0.62–4.11)	0.241, 1.91 (0.65–5.62)
GSTP1-MMP12	Ile/Ile-G/	8.2	11.0	1	1
	Val/-G/	9.8	16.0	0.740, 0.82 (0.26–2.57)	0.435, 0.60 (0.167–2.16)
	Ile/Ile-A/A	31.2	34.0	0.677, 1.23 (0.46–3.25)	0.884, 1.08 (0.37–3.16)
	Val/-A/A	50.8	39.0	0.247, 1.75 (0.68–4.50)	0.293, 1.75 (0.62–5.00)
MMP1-MMP9	G/G-C/C	14.7	25.0	1	1
	GG-C/C	52.5	47.0	0.080, 1.89 (0.93–3.86)	0.051, 2.21 (0.99–4.922)
	G/G-T/	9.0	7.0	0.174, 2.18 (0.71–6.72)	0.111, 2.80 (0.79–9.94)
	GG-T/	23.8	21.0	0.122, 1.92 (0.84–4.38)	0.081, 2.29 (0.90–5.83)
MMP1-MMP12	G/G-G/	6.5	14.0	1	1
	GG/-G/	11.5	13.0	0.280, 1.88 (0.60–5.96)	0.141, 2.60 (0.73–9.26)
	G/G-A/A	17.2	18.0	0.192, 2.04 (0.70–5.97)	0.096, 2.74 (0.84–9.00)
	GG/-A/A	64.8	55.0	0.053, 2.51 (0.99–6.40)	0.023, 3.33 (1.18–9.45)
MMP9-MMP12	C/C-G/	10.6	22.0	1	1
	T/-G/	7.4	5.0	0.091, 3.05 (0.84–11.07)	0.051, 4.39 (0.99–19.42)
	C/C-A/A	56.6	50.0	0.032, 2.33 (1.07–5.08)	0.020, 2.81 (1.18–6.70)
	T/-A/A	25.4	23.0	0.064, 2.28 (0.95–5.46)	0.041, 2.76 (1.04–7.32)

COPD, chronic obstructive pulmonary disease; GST, glutathione S-transferase; and MMP, matrix metalloproteinase.

^a Crude.

^b Adjusted for age, gender, and smoking status.

Table 3. The MMPs 1, 9, and 12 Variants in the Severity and Onset of COPD.

		FEV1, % pred				COPD onset, years
Gene	Genotype	<50, %	≥50, %	p, OR (95.5% CI)^a	p, OR (95.5% CI)^b	<40, %	≥40, %	p, OR (95.5% CI)^a	p, OR (95.5% CI)^c
		82 (67.2)	40 (32.8)			34 (27.7)	88 (72.3)
MMP1 rs1799750	G/G	23.2	25.0	1	1	14.7	27.3	1	1
	GG/	76.8	75.0	0.824, 1.10 (0.46–2.67)	0.934, 1.04 (0.42–2.59)	85.3	72.7	0.150, 2.17 (0.75–6.27)	0.057, 3.15 (0.97–10.23)
MMP9 rs3918242	C/C	63.4	75.0	1	1	64.7	68.2	1	1
	T/	36.6	25.0	0.203, 1.73 (0.74–4.03)	0.109, 2.09 (0.85–5.17)	35.3	31.8	0.714, 1.17 (0.51–2.69)	0.762, 1.15 (0.47–2.83)
MMP12 rs2276109	A/A	80.5	85.0	1	1	67.6	87.5	1	1
	G/	19.5	15.0	0.544, 1.37 (0.49–3.83)	0.531, 1.41 (0.48–4.19)	32.4	12.5	0.013, 3.35 (1.29–8.71)	0.025, 3.30 (1.16–9.40)

COPD, chronic obstructive pulmonary disease; FEV¹, forced expiratory volume in 1 second; and MMP, matrix metalloproteinase.

^a Crude.

^b Adjusted for age, gender, and smoking status.

^c Adjusted for gender and smoking status.

Table 4. Gene–Gene Interactions Among GSTM1 and MMPs 1, 9, and 12 in the Severity and Onset of COPD.

		FEV(1), % pred				COPD onset, years
Gene–gene interaction	Genotype	<50, %	≥50, %	p, OR (95.5% CI)^a	p, OR (95.5% CI)^b	<40, %	≥40, %	p, OR (95.5% CI)^a	p, OR (95.5% CI)^c
		82 (67.2)	40 (32.8)			34 (27.7)	88 (72.3)
GSTM1-MMP1	wt-G/G	7.3	12.5	1	1	5.9	10.2	1	1
	null-G/G	15.9	12.5	0.335, 2.17 (0.45–10.44)	0.281, 2.47 (0.48–12.79)	8.8	17.1	0.917, 0.90 (0.12–6.46)	0.833, 1.25 (0.15–10,36)
	wt-GG/	25.6	37.5	0.824, 1.17 (0.30–4.54)	0.835, 1.17 (0.27–4.96)	41.2	25.0	0.218, 2.86 (0.54–15.25)	0.084, 5.01 (0.80–31,28)
	null-GG/	51.2	37.5	0.210, 2.33 (0.62–8.78)	0.209, 2.47 (0.60–10.10)	44.1	47.7	0.571, 1.61 (0.31–8.30)	0.244, 2.88 (0.49–17,08)
GSTM1-MMP9	wt-C/C	24.4	37.5	1	1	38.2	25.0	1	1
	null-C/C	39.0	37.5	0.31, 1.60 (0.64–3.97)	0.269, 1.74 (0.65–4.61)	26.5	43.2	0.073, 0.40 (0.15–1.09)	0.132, 0.44 (0.15–1.28)
	wt-T/	8.5	12.5	0.943, 1.05 (0.28–3.96)	0.683, 1.33 (0.33–5.35)	8.8	10.2	0.447, 0.56 (0.13–2.47)	0.411, 0.51 (0.10–2.54)
	null-T/	28.1	12.5	0.039, 3.45 (1.06–11.16)	0.019, 4.83 (1.29–18.01)	26.5	21.6	0.679, 0.80 (0.28–2.29)	0.814, 0.87 (0.28–2.72)
GSTM1-MMP12	wt-G	3.7	0.0	1	1	14.7	2.3	1	1
	null-G	15.8	5.0	0.045, 8.67 (1.05–71.57)	0.038, 10.04 (1.14–88.46)	17.6	10.2	0.181, 0.27 (0.04–1.85)	0.196, 0.25 (0.03–2.03)
	wt-A/A	29.3	40.0	0.403, 2.00 (0.39–10.16)	0.377, 2.16 (0.39–1.91)	32.4	33.0	0.038, 0.15 (0.03–0.90)	0.041, 0.14 (0.02–0.92)
	null-A/A	51.2	45.0	0.163, 3.11 (0.63–15.34)	0.145, 3.54 (0.65–19.43)	35.3	54.5	0.010, 0.10 (0.02–0.58)	0.019, 0.11 (0.02–0.69)

COPD, chronic obstructive pulmonary disease; FEV¹, forced expiratory volume in 1 second; GST, glutathione S-transferase; and MMP, matrix metalloproteinase.

^a Crude.

^b Adjusted for age, gender and smoking status.

^c Adjusted for gender and smoking status.

Raherison C, Girodet PO. Epidemiology of COPD. Eur Respir Rev. 2009;18(114):213–221.

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