CYP1A1, GCLC, AGT, AGTR1 Gene - Gene Interactions in Community-acquired Pneumonia Pulmonary Complications

Molecular Biology Reports

Lyubov E. Salnikova, Dr. Sci. (Biol.)a,b,*, Tamara V. Smelaya, Dr. Sci. (Med.)b, Arkadiy M. Golubev, Dr. Sci. (Med.)b, Alexander V. Rubanovich, Dr. Sci. (Biol.)a, Viktor V. Moroz, Corresponding Member of Russian Acad. Med. Sci.b

aN.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkin street, Moscow 117971, Russia;

bV. A. Negovsky Research Institute of General Reanimatology, Russian Academy of Medical Sciences, 25 Petrovka str., build.2, Moscow, Russia107031

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Suppl. Table 3. The distribution of genotypes among CAP groups with and without extrapulmonary complications

Toxic shock syndrome (TSS) / Myocarditis
Genes and genotypes / Non - TSS / TSS / Adjusted analysisa / Non
myocarditis / Myocarditis / Adjusted analysis
Number (%) / P-valueb (genetic model)c, OR,
95% CI / Number (%) / P-value
(genetic
model), OR,
95% CI
CYP1A1
rs2606345 / n = 260 / n = 84 / 0.69 (dom)
1.13
0.63 – 2.01 / n = 291 / n = 53 / 0.63 (dom)
1.18
0.60 – 2.29
T/T / 145 (55.8) / 45 (53.6) / 162 (55.7) / 28 (52.8)
T/G / 89 (34.2) / 29 (34.5) / 99 (34.0) / 19 (35.9)
G/G / 26 (10.0) / 10 (11.9) / 30 (10.3) / 6 (11.3)
CYP1A1
rs4646903 / n = 260 / n = 84 / 0.65 (dom)
1.19
0.56 – 2.53 / n = 291 / n = 53 / 0.83 (dom)
1.10
0.46 – 2.63
T/T / 216 (83.1) / 68 (81.0) / 240 (82.5) / 44 (83.0)
T/C / 44 (16.9) / 15 (17.9) / 50 (17.2) / 9 (17.0)
C/C / 0 (0.0) / 1 (1.2) / 1 (0.3) / 0 (0.0)
CYP1A1
rs1048943 Ile462Val / n = 260 / n = 84 / 0.143 (dom)
1.56
0.53 – 4.59 / n = 291 / n = 53 / 0.74 (dom)
0.79
0.20 – 3.13
A/A / 234 (90.0) / 77 (91.7) / 261 (89.7) / 50 (94.3)
A/G / 26 (10.0) / 7 (8.3) / 30 (10.3) / 3 (5.7)
G/G / 0 (0.0) / 0 (0.0) / 0 (0.0) / 0 (0.0)
AhR
rs2066853
Arg554Lys / n = 254 / n = 82 / 0.20 (dom)
1.60
0.79 – 3.27 / n = 284 / n = 52 / 0.28 (dom)
1.56
0.70 – 3.45
G/G / 207 (81.5) / 62 (75.6) / 230 (81.0) / 39 (75.0)
G/A / 44 (17.3) / 20 (24.4) / 51 (18.0) / 13 (25.0)
A/A / 3 (1.2) / 0 (0.0) / 3 (1.1) / 0 (0.0)
GSTM1
Del(D/D)-
Ins (I/*) / n = 260 / n = 83 / 0.043 (N/A)
1.83
1.01 – 3.32 / n = 291 / n = 52 / 0.74 (N/A)
1.12
0.57 – 2.17
D/D / 111 (42.7) / 29 (34.9) / 118 (40.5) / 22 (42.3)
I/ / 149 (57.3) / 54 (65.1) / 173 (59.5) / 30 (57.7)
GSTT1
Del(D/D)-
Ins (I/*) / n = 260 / n = 83 / 0.4 5 (N/A)
1.35
0.62 – 2.98 / n = 291 / n = 52 / 0.15 (N/A)
2.05
0.73 – 5.78
D/D / 47 (18.1) / 12 (14.5) / 54 (18.6) / 5 (9.6)
I/ / 213 (81.9) / 71 (85.5) / 237 (81.4) / 47 (90.4)
ABCB1
rs1045642 Ile1145 = / n = 259 / n = 82 / 0.37 (rec)
0.69
0.31 – 1.56 / n = 290 / n = 51 / 0.11 (rec)
0.45
0.16 - 1.27
T/T / 108 (41.7) / 35 (42.7) / 120 (41.4) / 23 (45.1)
T/C / 106 (40.9) / 36 (43.9) / 119 (41.0) / 23 (45.1)
C/C / 45 (17.4) / 11 (13.4) / 51 (17.6) / 5 (9.8)
SOD2
rs4880
Ala16Val / n = 265 / n = 83 / 0.39 (rec)
1.35
0.68 – 2.70 / n = 294 / n = 54 / 0.83 (dom)
0.92
0.45 – 1.91
T/T / 76 (28.7) / 25 (30.1) / 86 (29.2) / 15 (27.8)
T/C / 129 (48.7) / 38 (45.8) / 140 (47.6) / 27 (50.0)
C/C / 60 (22.6) / 20 (24.1) / 68 (23.1) / 12 (22.2)
CAT
rs17880664 / n = 253 / n = 83 / 0.42 (dom)
0.78
0.43 – 1.41 / n = 284 / n = 52 / 0.76 (dom)
1.11
0.56 – 2.20
T/T / 92 (36.4) / 35 (42.2) / 107 (37.7) / 20 (38.5)
T/A / 129 (51.0) / 42 (50.6) / 142 (50.0) / 29 (55.8)
A/A / 32 (12.7) / 6 (7.2) / 35 (12.3) / 3 (5.8)
GCLC
rs17883901 / n = 253 / n = 82 / 0.50 (dom)
0.78
0.37 – 1.63 / n = 285 / n = 50 / 0.24 (dom)
0.58
0.23 – 1.47
C/C / 200 (79.0) / 67 (81.7) / 224 (78.6) / 43 (86.0)
C/T / 52 (20.6) / 15 (18.3) / 60 (21.1) / 7 (14.0)
T/T / 1 (0.4) / 0 (0.0) / 1 (0.4) / 0 (0.0)
ACE
rs4340
Alu-287 bp / n = 260 / n = 84 / 0.26 (dom)
1.42
0.77 – 2.64 / n = 291 / n = 53 / 0.80 (dom)
0.92
0.46 – 1.83
D/D / 92 (35.4) / 25 (29.8) / 99 (34.0) / 18 (34.0)
I/D / 111 (42.7) / 32 (38.1) / 127 (43.6) / 16 (30.2)
I/I / 57 (21.9) / 27 (32.1) / 65 (22.3) / 19 (35.9)
AGT
rs699
Met235Thr / n = 257 / n = 81 / 0.39 (rec)
0.73
0.36 – 1.51 / n = 289 / n = 49 / 0.67 (dom)
0.85
0.41 – 1.77
T/T / 80 (31.1) / 26 (32.1) / 90 (31.1) / 16 (32.6)
T/C / 113 (44.0) / 40 (49.4) / 130 (45.0) / 23 (46.9)
C/C / 64 (24.9) / 15 (18.5) / 69 (23.9) / 10 (20.4)
AGTR1
rs5186 / n = 259 / n = 82 / 0.20 (rec)
1.97
0.71 – 5.48 / n = 290 / n = 51 / 0.11 (rec)
2.54
0.84 – 7.73
A/A / 152 (58.7) / 42 (51.2) / 170 (58.6) / 24 (47.1)
A/C / 89 (34.4) / 31 (37.8) / 100 (34.5) / 20 (39.2)
C/C / 18 (7.0) / 9 (11.0) / 20 (6.9) / 7 (13.7)
MTHFR
rs1801133 Ala222Val / n = 258 / n = 83 / 0.11 (rec)
2.16
0.85 – 5.51 / n = 289 / n = 52 / 0.53 (dom)
1.24
0.62 – 2.42
C/C / 113 (43.8) / 35 (42.2) / 127 (43.9) / 21 (40.4)
C/T / 120 (46.5) / 36 (43.4) / 130 (45.0) / 26 (50.0)
T/T / 25 (9.7) / 12 (14.5) / 32 (11.1) / 5 (9.6)
NOS3
rs1799983 Glu298Asp / n = 260 / n = 82 / 0.32 (rec)
1.79
0.57 – 5.65 / n = 291 / n = 51 / 0.89 (dom)
1.05
0.54 – 2.04
G/G / 151 (58.1) / 45 (54.9) / 169 (58.1) / 27 (52.9)
G/T / 94 (36.1) / 30 (36.6) / 102 (35.0) / 22 (43.1)
T/T / 15 (5.8) / 7 (8.5) / 20 (6.9) / 2 (3.9)
VEGF-α
rs833061 / n = 259 / n = 80 / 0.37 (dom)
0.74
0.39 – 1.42 / n = 288 / n = 51 / 0.77 (dom)
0.89
0.42 - 1.88
C/C / 69 (26.6) / 24 (30.0) / 79 (27.4) / 14 (27.4)
C/T / 135 (52.1) / 37 (46.2) / 147 (51.0) / 25 (49.0)
T/T / 55 (21.2) / 19 (23.8) / 62 (21.5) / 12 (23.5)

aAdjusted analysis by age, sex, co-morbidity, PSI and causative microorganism;

bGenotypes associated with response in the accordance with OR (protective, if OR<1, susceptible, if OR>1) are highlighted in grey; significant P-values are in bold;

cThe genetic model: rec - recessive, dom - dominant