Genetic Polymorphisms in NLRP3 Inflammasome-Associated Genes in Patients with B-Cell Non-Hodgkin’s Lymphoma

Figures & data

Table 1 The Base Information of Patients with B-NHL in This Study

Characteristics		Case (n)	Percentage (%)
Age/year	≤ 60 y	175	62.28
	> 60 y	106	37.72
Sex	Male	155	55.16
	Female	126	44.84
Stage	I–II	53	18.86
	III–IV	228	81.14
LDH (U/L)	<230	157	55.87
	≥230	124	44.13
Extranodal involvement	0~2	196	69.75
	≥2	85	30.25
Bone marrow involvement	(–)	244	86.83
	(+)	37	13.17
B symptoms	(–)	206	73.31
	(+)	75	26.69
IPI	0~2	185	65.84
	3~5	96	34.16
Pathologic type	DLBCL	188	66.90
	FL	48	17.08
	MCL	15	5.34
	MZL	17	6.05
	Others	13	4.63

Table 2 The Distribution of NLRP3 Genetic Polymorphisms and Their Association with B-NHL Susceptibility

Polymorphisms	Case (n)	Control (n)	χ^2	P
IL-18 (rs1946518)
GG	187 (69.78%)	104 (27.01%)	122.789	<0.0001
GT	71 (26.49%)	203 (52.73%)
TT	10 (3.73%)	78 (20.26%)
IL-1β (rs16944)
GG	83 (29.75%)	100 (25.97%)
GA	131 (46.95%)	189 (49.09%)	1.1692	0.5574
AA	65 (23.30%)	96 (24.94%)
CARD8 (rs2043211)
AA	65 (26.21%)	118 (30.65%)	1.5652	0.4572
AT	115 (46.37%)	172 (44.68%)
TT	68 (27.42%)	95 (24.67%)
NFκB-94 (ins/del ATTG)			11.7041	0.0029
ins/ins	116 (43.28%)	119 (30.91%)
ins/del	100 (37.31%)	189 (49.09%)
del/del	52 (19.40%)	77 (20.00%)

Note: Statistical significant P values and corresponding lines are displayed in bold.

Table 3 The Distribution of NLRP3 Genetic Polymorphisms and Their Association with DLBCL and FL Susceptibility

Polymorphisms	Control (n)	DLBCL			FL
		Case (n)	χ^2	P	Case (n)	χ^2	P
IL-18(rs1946518)
GG	104(27.01%)	132(71.74%)	106.3	<0.0001	31(65.96%)	30.51	<0.0001
GT	203(52.73%)	46(25.00%)			14(29.79%)
TT	78(20.26%)	6(3.26%)			2(4.25%)
IL-1β(rs16944)
GG	100 (25.97%)	54 (29.19%)	1.053	0.5906	17(35.42%)	4.311	0.1159
GA	189(49.09%)	91 (49.19%)			16(33.33%)
AA	96(24.94%)	40 (21.62%)			15(31.25%)
CARD8(rs2043211)
AA	118(30.65%)	44(27.33%)	0.784	0.6757	12(26.09%)	2.2	0.3329
AT	172(44.68%)	78(48.45%)			18(39.13%)
TT	95(24.67%)	39(24.22%)			16(34.78%)
NFκB-94(ins/del ATTG)
ins/ins	119(30.91%)	83(45.86%)	12.67	0.0018	17(36.17%)	0.772	0.6797
ins/del	189(49.09%)	65(35.91%)			20(42.55%)
del/del	77(20.00%)	33(18.23%)			10(21.28%)

Note: Statistically significant P values and corresponding lines are displayed in bold.

Table 4 The Distribution of NLRP3 Alleles and Their Association with B-NHL Susceptibility

Alleles	Case (n)	Control (n)	χ^2	P	OR (95% CI)
IL-18 (rs1946518)
G	445 (83.02%)	411 (53.38%)	123.00	<0.0001	4.271 (3.273–5.574)
T	91 (16.98%)	359 (46.62%)
IL-1β (rs16944)
G	297 (53.23%)	389 (50.52%)	0.9489	0.33	1.115 (0.8960–1.386)
A	261 (46.77%)	381 (49.48%)
CARD8 (rs2043211)
A	245 (49.40%)	408 (52.99%)	1.5581	0.2119	0.8660 (0.6909–1.086)
T	251 (50.60%)	362 (47.01%)
NFκB-94(ins/del ATTG)
ins	332(61.94%)	427 (55.45%)	5.4612	0.0194	1.265 (1.010–1.586)
del	204(38.06%)	343 (44.55%)

Note: Statistically significant P values and corresponding lines are displayed in bold.

Table 5 The Distribution of NLRP3 Genetic Polymorphisms and Their Association with Clinical Features of B-NHL

NLRP3			IL-18			IL-1β			CARD8			NFκB-94
Genetic Polymorphisms			GG	GT	TT	GG	GA	AA	AA	AT	TT	ins/ins	ins/del	del/del
Age (years)		<60	114	46	6	50	75	40	44	64	39	71	57	31
		≥60	80	26	4	33	55	25	21	50	29	45	45	22
χ^2			0.5757			0.3044			2.475			0.6355
P			0.7499			0.8588			0.2902			0.7278
Sex		Male	107	41	5	43	72	39	41	65	31	66	59	25
		Female	88	31	5	40	59	26	24	50	37	50	44	28
χ^2			0.2063			0.9949			4.253			1.697
P			0.902			0.6081			0.1193			0.4281
LDH (U/L)		<230	111	40	4	43	74	39	37	57	46	63	54	37
		≥230	82	32	5	38	56	26	27	56	22	53	47	16
χ^2			0.6386			0.7157			5.147			4.407
P			0.7267			0.6985			0.0763			0.1104
Stage		I-II	33	16	2	13	21	17	12	15	18	24	14	13
		III-IV	160	56	2	68	109	48	52	98	50	92	87	40
χ^2			3.442			3.326			4.939			3.012
P			0.1789			0.1896			0.0846			0.2218
Extranodal involvement		0~2	180	63	9	74	121	58	58	101	64	105	94	50
		≥2	13	8	1	9	8	6	6	12	4	10	7	3
χ^2			1.498			1.543			1.182			0.7613
P			0.4728			0.4623			0.5537			0.5454
IPI		0~2	130	48	6	52	87	45	45	68	49	76	65	38
		3~5	65	24	4	31	44	20	20	47	19	40	38	15
χ^2			0.1921			0.7264						1.156
P			0.9084			0.6955			0.1536			0.5611

Note: IPI: R-IPI for DLBCL, FLIPI for FL, MIPI for MCL, and IPI for others.

Figure 1 Kaplan-Meier curves of IL-18 (rs1946518), IL-1β (rs16944), CARD8 (rs2043211) NFκB-94 ins/del ATTG genotypes and LDH in patients with B-NHL. Log-rank P values compared with the different genotypes are shown, and CARD8 (rs2043211) AA genotype and higher LDH contributed to poorer B-NHL survival.

Table 6 Cox Regression Analysis for Survival of Patients with B-NHL

Factors	P	HR	95.0% CI for HR
			Lower	Upper
Pathologic
Aggressive	0.920	1.032	0.562	1.893
LDH(U/L)
≥230	0.780	1.098	0.570	2.114
IPI
3~5	0.030	2.101	1.075	4.098
NFκB-94(ins/del ATTG)
del/del	0.260	1.000
ins/ins	0.388	1.495	0.599	3.729
ins/del	0.121	2.040	0.829	5.019
IL-18(rs1946518)
TT	0.846	1.000
GG	0.633	1.626	0.222	11.936
GT	0.733	1.433	0.181	11.321
IL-1β(rs16944)
GG	0.944	1.000
AA	0.756	0.878	0.386	1.997
GA	0.778	0.907	0.461	1.785
CARD8(rs2043211)
TT	0.401	1.000
AA	0.226	1.618	0.742	3.525
AT	0.750	1.128	0.538	2.366

Note: Statistically significant P values and corresponding lines are displayed in bold.